Treatment of keratoconus by Collagen Cross-Linking
Over the past 10 years, the use of topical riboflavin combined with ultraviolet A (UVA) irradiation to increase collagen cross-linking (CXL) has demonstrated the potential for retarding or eliminating the progression of keratoconus and corneal ectasia.
What is corneal collagen cross-linking?
Corneal collagen cross-linking (CXL) is a new, noninvasive treatment for keratoconus. CXL involves applying a photosensitizing solution consisting of Riboflavin (vitamin B2) to the cornea and exposing it to a low dose of ultraviolet light. The photosensitizer reacts with the ultraviolet light to create new collagen bonds (cross-links) throughout the cornea.
In corneas affected by keratoconus there are too few collagen bonds to maintain structural integrity. The reduced number of collagen bonds and weakened configuration result in corneal bulging, steepening, and irregularity all of which significantly affect vision.
By creating new collagen bonds, CXL strengthens and adds resilience to corneas weakened by keratoconus. If performed early enough, CXL can counteract its effects and allow good vision to preserved. In advanced cases, CXL can postpone the need for invasive corneal transplants and prevent vision from getting worse.
How is the treatment done?
CXL is a straightforward and painless procedure performed in a treatment room under topical anaesthesia. During treatment, the upper-most layer of the cornea (called the epithelium) is gently scraped off to allow for absorption of the photosensitizing agent. Next,riboflavin drops and ultraviolet light are applied for a period of 6, 9, 20 or 30 minutes. Once the procedure is complete, the eye is covered with a bandage contact lens to help the epithelium grow back (usually within 2 to 3 days) and facilitate a quick visual recovery.
Can ultraviolet light harm my eyes?
Ultraviolet light used for the CXL treatment was specifically selected to be safe on the cornea, lens and retina while still being sufficient to induce collagen cross-linking. Laboratory and clinical studies have demonstrated that the amount of light that reaches the deeper structures in the eye is not strong enough to cause damage. Furthermore, the ultraviolet light is measured and calibrated prior to each
treatment to ensure that safe exposure levels are never exceeded.
When will I notice changes?
Within one week vision returns to prior levels. The most dramatic improvements tend to occur during the first three months and then, gradually over a period of up to one year, the cornea continues to stiffen and stabilize resulting in further improvements. In most cases, the keratoconus stops getting worse and in some cases vision improves.
How long is follow-up?
You will be seen shortly after the procedure to remove the bandage contact lens and assess your recovery. Regular follow-up visits will be at one, three and six months, and at one year. After that you will be seen anually to monitor your results.
When can I wear contact lenses again?
In most cases, you may return to wearing contact lenses after months. However, your contacts may need to be changed occasionally until your cornea fully stabilizes.
CXL failure is largely defined as keratoconic progression following treatment.
Reactivation of HSV has been reported after emotional stress, trauma, fever, and laser surgery. These established clinical triggers are thought to be mediated by the adrenergic and sensory nervous systems. Exposure to UV light can also induce oral and genital herpes in humans and ocular herpes in animal models. Development of herpes keratitis and iritis after riboflavin-UVA treatment has been reported.
Sterile corneal stromal infiltrates occur as a result of enhanced cell-mediated immunity to staphylococcal antigens deposited at high concentrations in areas of static tear pooling.
Keratitis can occur following CXL because of presence of an epithelial defect, use of soft bandage contact lens, and topical corticosteroids in the immediate postoperative period. In cases of corneal infection after CXL, contact with the infectious agent likely occurred during the early postoperative period rather than during surgery because CXL not only damages keratocytes, but it also kills bacteria and fungi. This effect is used to advantage when CXL is performed for infectious keratitis.
Approximately 9% of the 127 patients developed clinically significant corneal haze after 1-year followup.
The haze after CXL differs from the haze after PRK in stromal depth. Whereas haze after PRK is strictly subepithelial, haze after CXL extends into the anterior stroma to approximately 60% depth, which is on average equal to an absolute depth of 300 μm. Haze after CXL is different in clinical character from haze after other procedures, such as excimer laser photorefractive keratomy. The former is a dustlike change in the corneal stroma or a midstromal demarcation line, whereas the latter has a more reticulated subepithelial appearance The haze may be associated with the depth of CXL into the stroma as well as the amount of keratocyte loss What makes corneal collagen cross-linking unique?
CXL is a unique treatment because it is noninvasive and targets the root of the problem which is the weakened cornea in keratoconus.
CXL significantly increases the number of collagen bonds between the corneal layers, in effect returning the cornea to a more stablestate. In contrast to other procedures like intrastromal ring segments or laser surgery, CXL offers the potential to target the underlying cause and thus offer long-term benefits for those suffer from keratoconus.
More interestingly, CXL can be a part of a process in the management of keratoconus patients. It can be combined with corneal rings before or after the procedure, and « fine tuned » with surface laser procedures.
Repeat cross-linking treatments may become necessary in the long term. Considering that the turnover rate of stromal collagen fibres is several years, prospective studies with a followup of at least eight to ten years will be necessary.