1) What is it?                                                                                                  

It is the use of carefully controlled amounts of ultra-violet light applied for a fixed amount of time (30 minutes) using yellow riboflavin dye (vitamin B2 commonly used in food). Riboflavin serves two purposes: on one hand, it generates the cross-links via the formation of free radicals in conjunction with UVA irradiation. On the other hand, it protects the deeper layers of the eye from excessive amounts of UVA light (riboflavin shielding).
 

2) How does it work?

By inducing additional molecular bonds between the collagen fibers of the cornea. Interestingly, this phenomenon also occurs during the natural ageing process. This might be a reason why keratoconus usually stops its progression at a certain age.

3) How safe is it?

Very. There are no cuts in the body of the cornea. To quote Theo Seiler, who is one of the developers: ‘David, if it was my son who had Keratoconus I would treat him tomorrow!’ It is much safer than a corneal graft which has been very successful in the past, and even than a gas permeable contact lens, and also there is no chance of rejection (grafts tend to last 10-15 years), minimal chance of infection and minimal chance of significant scarring.  The ultra-violet exposure is less than from a day walking in the Welsh mountains.

The transplant carries risks such as infection, rejection and astigmatism. Crosslinking avoids the removal of any corneal structural tissue (only the surface epithelial cells are removed and these grow back within 2 days).

 

4) What treatment units are there and how do they differ?

IROC (the original German-Swiss unit), Priavision Keracure - developed in the US (can be used to treat both eyes at once but this is not advised) and the CBM X LINKER developed in Italy. All require riboflavin drops to be applied to the eye first. In the IROC system the aperture can be adjusted for eye size, but is nearly always set to medium making it about 8mm diameter on the cornea. It also emits the UV light via a special optical System (Koehler optics) that makes the unit much less responsive to slight variations in illumination distance. This way, the risk of overexposure is minimized. In all the systems UV light at a wavelength of 365-370nm is applied to the cornea. In the IROC system 7 light emitting diodes are set in a flower pattern. This gives a very smooth distribution of light over the cornea. The original systems used 1 or 2 lights and the results were not as good as they could produce damaging hot spots. The CBM X LINKER system uses 5 diodes. The IROC and CBM X LINKER systems are mounted on stands. The Priavision system sits on a loupe around the head, so that if the patient moves the distance does not change. Only the IROC system was CE approved by January 2007 but others were awaiting approval then.

5) What is it used for?

Keratoconus, Pellucid Marginal Degeneration, Laser Eye Surgery (PRK, LASIK or LASEK) post-surgical ectasia and regression, Conductive Keratoplasty regression (used to treat the need for reading glasses), corneal melting, whether it is infectious or non-infectious (ultra-violet light kills bacteria, decreases the activity of kollagenases) and other rarer conditions.

The following procedures are still experimental: It may also be used to stiffen corneas before corneal transplant surgery so making the surgery easier, and it has been suggested that it could be used as a safety treatment before LASIK so that corneal ectasia (bulging) does not occur afterwards and to correct RK patients who have gone long sighted.

6) Who is suitable and who is not?

People with over generally 0.400mm thick corneas after removal of the epithelium (under special circumstances, also thinner corneas can be treated using hyposomolar riboflavin solution to thicken the cornea preoperatively), keratometry readings of less than 60D, no severe central scarring, no history of Herpes Simplex or Zoster eye infections or scars, generally under 40 years old for Keratoconus (but not other conditions) and not pregnant (because of variable healing).

Although the method is very promising, IROC in Switzerland only recommends treatment once a clear progression has been documented on the same topgraphical device. IROC does not recommend prophylactic treatments at this time.
 

 
7) Are there any age limits?

No. Keratoconus develops at puberty at the earliest which produces a natural age limit. At our centre in London we have treated people as young as 12. Treatment for those above 40 is uncommon for Keratoconus although it may be successful, but it may be useful for other conditions such as Pellucid Marginal Degeneration, Keratectasia after LASIK surgery, and prolonging the Effect of Conductive Keratoplasty in the over 40’s.

8) How is it done?

After application of anesthetic drops, surface cells (the epithelium) are rubbed off the eye with a blunt instrument (so that it is not cut). A spring keeps the lid open so that the riboflavin dye can be applied for 30 minutes with saline to keep the eye wet in between, the eye is checked to see that the dye has soaked in, the ultra-violet is applied for 30 minutes with the riboflavin drops still being applied every few minutes.

A bandage contact lens soaked in antibiotic solution and protective pad are applied overnight to reduce discomfort and minimize risk of infection, and drops are used for 3 weeks afterwards to reduce the risk of infection also.

It is important that the patient looks at the violet light to keep the effect central, but some movement is inevitable and not a problem. For the 30 mins of UV light application the doctor must keep the light ring in focus. If it is too close the doctor will see 7 spots of light with the IROC system and if it is too far away the circle edge becomes blurred.

9) What are the possible complications and side effects?

Pain in the first 1-2 days, sensitivity to light for several days, haze causing blurring (some describe it as making the vision a bit ‘milky’) for up to a few weeks which may require drops. The temperature rise of the cornea is significantly less than required to cause thermal damage to the collagen protein which makes up the cornea. Occasionally people have felt pain very briefly some weeks later a bit like with a contact lens.

10) How much treatment is needed?

There is only one treatment level at present: 30 mins of 3.0mW/cm2. This was found to be optimal for effect and safety and IROC machines can not now be adjusted to prevent the risk of errors. All systems use the same protocol.

11) Can it be combined with other treatments?

Yes. For example intrastromal corneal rings (eg Intacs, Ferrara or Bisantis), Phakic Lens Implants, Refractive Lens Exchange, ARK, PRK or LASEK to reduce both astigmatism and short sight. Generally these are done in steps and may be separated by some months. All these procedures in addition are promising but have no long-term results yet.

12) Can it be redone if needed?

Yes, but it has not been needed yet within the guidelines used. The collagen cells have a very slow turnover rate so any re-treatment may need to be done 10-20 years later if at all. The age of 40 can be thought of as a rough finishing line. By and largely then natural crosslinking associated with age should stop further progression.

13) Can I wear contact lenses after treatment if I need?

Yes, that is one of the main aims. Rigid gas permeable lenses are good for vision in Keratoconus, but can cause central scarring in some cases. By making a cornea more regular a simpler contact lens can be used; for example a soft toric one. This can be worn as soon as four weeks after surgery, as it may possibly affect healing if worn earlier. As 40% of all cross-linked patients show an improvement of the maximal steepness of the cornea at 6 months after treatment, the contact lens geometry might need to be adjusted at that time.

14) Are there any limitations in what I can do after surgery?

There are no limitations to lifting as there are no cuts. You should avoid getting the eye wet for a few days afterwards and avoid wearing a contact lens as long as 4 weeks, as it may possibly affect healing. The blurring mentioned before may affect some people, especially in the first few days, which may limit work and driving.

15) Is it visible afterwards?

No. There is no change in appearance or colour.

 
16) How many have been done?

A few thousand and by the end of this year, it will be many more as so many doctors are convinced of its benefits.

17) How long ago was the first one done?

The first human eyes were treated in 1998. The very first eyes were blind, so that if anything unexpected occurred there would be no serious damage caused. The Germans and Swiss are very cautious! These have all been carefully followed and none has worsened since.

 

18) Has it been fully approved?

It was fully approved for use in the EU in January 2007 and has been used experimentally in the US while being researched by the FDA. Approval is expected soon.

19) Can you feel it afterwards?

Once the surface has fully healed after a few days the eye should not feel any different from normal.

20) Can both eyes be done at the same time?

Technically yes, but the blurring makes this impractical. It can be done if the surface cells (epithelium) are not removed. It is normally done at least 1 week apart in the two eyes.

21) Does it make any other later treatments more difficult?

No. It has no effect on any future surgery as far has been determined until now. It does not prevent or complicate eye surgery for any other problems such as glaucoma or cataracts which may be needed later in life.

22) Is it likely to become more common?

Yes, hugely and rapidly. The only difficulty is how long each procedure takes (about 75 minutes with cell removal, riboflavin drops for 30 minutes, eye check, UV application 30 minutes and application of the bandage lens and/or eye pad).

Corneal collagen crosslinking has so many potential uses and so few side effects and complications that it is being taken up at a very rapid rate by doctors. If it fulfills its promise of saving many patients from corneal transplants then it will be a very great advance.

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