COLLAGEN CROSS-LINKING FOR KERATOCONUS AND CORNEAL ECTASIA

Diagnosis of Keratoconus is based on thinning of the cornea at the apex of the cone (found on slit-lamp examination) and corneal topographic and keratometric assessment of the curvature of the cornea. Keratoconus commonly affects children and young adults. This stretching or bulging of the cornea tends to progress but the rate at which it does varies. It usually affects both eyes, but sometimes one eye may be more affected while the other eye shows very little sign of the condition.

The first line of treatment is usually with rigid contact lenses, although some people with early Keratoconus may be able to wear spectacles or soft contact lenses. Good vision in patients with Keratoconus may be difficult to maintain, as the disease progresses and contact lens tolerance varies. As the disease progresses, spectacles or contact lenses may not be sufficient to correct visual acuity. Lamellar keratoplasty or penetrating keratoplasty may be required for severe progressive forms of the disease.

Recently, corneal collagen cross-linking has emerged as a promising technique to halt progression of Keratoconus.

What is collagen cross-linking?

First developed in Germany in 1998 and progressively improved on since then corneal collagen crosslinking (C3R or UV-X) uses ultraviolet light and riboflavin eye drops (vitamin B2) to stiffen the cornea. It works by cross-linking the protein fibres in the cornea to each other and within themselves. This procedure has been used in the early stages of Keratoconus as a way of halting the progression of the disease. Collagen cross-linking mimics the corneal stiffening which occurs naturally with ageing. This is the reason why Keratoconus does not usually progress in people aged 50 and over.

What does the procedure involve?

The procedure is performed as an outpatient procedure under topical anaesthetic eye drops. A micro eyelid clip is placed to keep the eye open during procedure. The epithelium is first abraided with a blunt spatula to allow the penetration of riboflavin into the corneal tissue. Riboflavin eye drops are applied frequently to the corneal surface while the cornea is exposed to 30 minutes of ultraviolet-A radiation. A soft bandage contact lens is placed on the eye at the end of the procedure.

What happens after the procedure?

Eye drops are prescribed after the treatment.

The soft contact lens is kept on the eye until the surface of the eye has healed (usually 5 to 7 days). The eye is gritty, red, and light sensitive for several days afterwards. The discomfort is worse on the second day, with gradual improvement thereafter.

The vision is blurred initially as the cells on the surface of the eye heal and while the pupil dilating drops are used to comfort the eye. In the first few weeks the cornea is usually swollen and this contributes to the reduced vision. The vision however usually continues to slowly improve for several months after the treatment.

What are the benefits of corneal cross-linking and how well does it work?

Collagen cross-linking is the only treatment currently available to stop the progression of Keratoconus. It has been performed around the world for 8 years, and over the past 3 years has been approved internationally in the European Union Countries and the whole of the Asia-Pacific region. Approval is awaited in the USA. Halting progression of Keratoconus is the crucial benefit of collagen cross-linking. Its main purpose is to stabilize the Keratoconus, not necessarily to improve the vision.

Most studies have reported a stabilization of the Keratoconus disease process compared with the pre- treatment state and this can last from 2 – 6 years. The evidence indicates that 12 months, after the procedure the corneal curvature decreases by an average of 1.5 dioptres in 100% of keratoconic eyes that have been treated, compared to a progressive increase in curvature by 1.3 dioptres in eyes that have not been treated. This data provides compelling evidence that the treatment is effective.

About half of eyes that have undergone cross-linking also achieve improvement in their corrected vision. In up to 60% of patients an improvement in best spectacle-corrected vision of at least 1 line on the Snellen vision chart can be observed. In some patients, uncorrected vision has improved by 3 lines. In the remaining patients, no improvement in vision was achieved.

Corneal cross-linking is also useful for ectasia of the cornea following LASIK, surgery, for pellucid marginal degeneration and other corneal ectatic disorders.

Patients with Keratoconus who are not able to wear contact lenses are also likely to benefit from early collagen cross-linking to stabilize the Keratoconus.

What are the risks of the procedure?

Severe complications associated with corneal cross-linking are uncommon (probably in the order of 1 – 2% of cases). It is important that patients have enough information about possible complications to fully weigh up the risks and benefits of the procedure. The main risks associated with corneal cross-linking are:

Corneal infection: Unusual infections, not responsive to standard post-operative antibiotic eye drops, have been reported in anecdotal cases. Reactivation of herpes simplex virus in the cornea has been reported following corneal cross-linking, similar to cases occurring after LASIK surgery. Severe corneal infection may cause permanent visual distortion due to corneal scarring. A corneal transplant may then be required.

Corneal inflammation and (very rarely) melting of the cornea: This has been reported in anecdotal cases and usually resolves with treatment.

Corneal haze: This causes visual “ghosting”, glare and halos, and blurriness especially in dim light. It occurs in up to 11% of cases in the first 3 months post-operatively. It usually resolves after 1 – 2 months, and has not been reported beyond 12 months.

Need for a repeat cross-linking treatment: More than one cross-linking treatment may be necessary, if the Keratoconus is found to be progressing.

Damage to the corneal endothelium, lens, retina: If the central cornea is less than 400µm thick, there is a theoretical risk of damage to the corneal endothelium (this is delicate cell layer lining the back of the cornea, which is vital to corneal clarity; corneal endothelial cells continually pump fluid out of the cornea, to maintain its clarity and prevent a water-logged or thickened cornea). There is also a possible risk of damage to intra-ocular structures such as the lens and retina by the UV light radiation. The riboflavin eye drops themselves absorb UV light, and thus protect the endothelium and intra-ocular structures. Hypotonic eye drops are used to swell the cornea if it is thinner than 400µm, and thus avoid potential damage to the corneal endothelium. There have been no reports of endothelial damage or damage to the lens or retina after corneal cross-linking so far. The total UV exposure to the eye during cross-linking is similar to a day’s mountain walking.

Recurrent corneal erosions (these may cause pain or prickling) There is a theoretical risk of a recurrent corneal erosion, because the corneal surface epithelial cells are dislodged and abraded during the cross-linking procedure. The epithelium normally heals in 3 to 7 days, but if the bonding between the surface epithelium and the underlying corneal stroma is weak, the epithelial cells won’t adhere properly and an epithelial defect will result. There may as a result be slight prickling symptoms for a number of months. These erosions usually resolves with use of a lubricating eye gel and ointment at bedtime.

Corneal scarring or increased corneal astigmatism: There is a theoretical risk of corneal scarring or increased corneal astigmatism occurring following the treatment (independent of any infection). This may cause permanent visual distortion which may require a corneal transplant.

The Practicalities of the Treatment:

Collagen cross-linking is a day case procedure, done under topical anaesthetic. The procedure takes at least 1 hour per eye.

It would be a good idea if you bring an IPod or other audio equipment with headphones to keep you relaxed and comfortable while waiting for the procedure to be completed.

You do not need to stay in hospital overnight after surgery.

Regular oral analgesics, cool compresses over the eyes and chilled eye drops will help control pain in the first few days.

The eyes will be light-sensitive for several days.

It will be safe to resume RGP contact lens wear once the epithelium has healed.

After the Treatment:

The visual recovery after corneal cross-linking can be slow; your vision may be blurred for several weeks.

You will need to take at least 5 days off work following the procedure. You will not damage the eye if you use it soon after the surgery, but keeping the eye closed will encourages it to heal.

The fluctuations in your vision can result in mild headaches.

Dusty environments are unlikely to damage the eye, but may be irritating, and should be avoided for 2 weeks after the surgery. If dust, dirt or an eyelash gets into your eye, wash these out with an eye drop.

Wear sunglasses for comfort and protection for at least 6 months, especially when outdoors.

Do not rub the eyes after the procedure; rubbing the eye may cause progression of the keratoconus and should be avoided in all circumstances.

Put an artificial tear drop in the eye if the eye feels itchy or irritated.

Other limitations on your activity for the first week include running, aerobics or gym exercises (in case of injury or sweat running into the eyes).

Do not use eye make up for a week after surgery.

Try not to get water or shampoo in your eyes in the shower or when washing your face (dab very gently with towel if you do).

It is also strongly advised that you do not fly any long haul flights within the first week.

For the first 2 to 4 weeks you should not swim in chlorinated water, play rugby or contact sports (boxing, kick-boxing) where there may be a direct blow to the eye. Chlorinated pools can irritate the eyes and public pools are usually contaminated. Wear goggles when swimming.

You can play golf, tennis, badminton etc. after a week. Scuba diving can be resumed after a month.

You can drive once you can read a number plate at 25 metres. If you are in doubt, your ophthalmologist will make sure that your vision is adequate to drive. Driving with good vision in only one eye is legal, but you should obviously exercise caution until you feel confident; start off by driving short distances by day in familiar surroundings.

It is important to contact your ophthalmologist if you experience severe pain, increasing (rather than decreasing) redness of the eye or progressive worsening (rather than improvement) of vision after the surgery.