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Corneal Cross-Linking (CXL)

Cross-linking is a method that appeared in many country relatively recently, but it has been used all over the world since 2004. Corneal collagen crosslinking is also known as crosslinking method, CXL method, UV-x-linking, UVA method, C3-R. Its Essence consists in photopolymerization of stromal fibers, which occurs under the combined action of a photosensitizing substance (Riboflavin or vitamin B2) and ultraviolet.

During recent years, there has been a noticeable expansion of cross-linking. For example, it is successfully used to prevent the progression of secondary keratoconus (arising after LASIK iatrogenic keratoectasia), pellucid marginal dystrophy, keratomalacia of various origins. There are preliminary encouraging data on the successful use of cross-linking for the treatment of bullous keratopathy, keratitis and corneal ulcers.

The history of the method

The beginning studies of the photobiology of the cornea refers to 1990. Then a group of researchers has been seeking biological adhesives, activated with heat or light, which reinforce the resistance of the collagen of the cornea (Khaderm, T. Tuong, T. J. Emest, 1994). A bonding effect was found to occur in the elimination of oxygen radicals, the release of which caused the formation of bonds of disparate collagen fibrils.
In the opinion of the researchers, the increased resistance of the tissues of the cornea stop the progression of keratoconus and, therefore, postpones or allows you is to avoid transplantation of the cornea patients.
Pioneers of crosslinking were: Professor T. Zeiler, E. Sporl, Wollensak. The idea of this method arose from Professor Zeiler during a visit to the dentist, after he was put photopolymer seal. In 1994, he led a team of researchers, and work began. The first experiments were carried out on animals, and then – on the donor (cadaver) cornea. After that, the first treatment of patients with keratoconus and other keratoectasia was carried out.

The mechanism of corneal cross-linking

  1. Combined effect of Riboflavin and UltraViolet;
  2. Release of oxygen radicals;
  3. The occurrence of coupling between the carbon base – collagen crosslinking.

The principle of operation of the method of corneal crosslinking in keratoconus (CXL)

Photopolymerization increases the strength of corneal collagen (rigidity) and increases its resistance to keratoectasia. Between collagen fibrils appear new cross-linking, and it increases the strength of the entire cornea.

Indications for CXL

Due to the relative youth of the method and the development of scientific thought, the scope of cross-linking is growing from year to year, its effectiveness is revealed with an increasing number of diseases. Therefore, we present the testimony formulated by Professor Seiler himself at the cross-linking courses during the international Congress in Berlin in September 2008. The crosslinking is recommended in cases:

  • keratoconus (KC);
  • pellucid marginal dystrophy (PMD);
  • iatrogenic keratoectasia due to LASIK surgery;
  • кkeratomalacia-melting of the cornea (cornea melting), which occurs, as a rule, due to autoimmune processes;
  • bullous keratopathy

Riboflavin for corneal cross-linking


  • the thickness of the cornea is less than 400 microns in at least one dimension (although it should be noted that this threshold has ceased to be so categorical after the appearance of solutions causing edema of the cornea);
  • low visual acuity with correction in the case of keratoconus, even in the presence of adequate thickness of the cornea;
  • patient's age is less than 12 years (not olways);
  • corneal scars on huge area;
  • allergic conjunctivitis.


Manipulations are carried out under local anesthesia (drops of Alkaine). Currently, two main techniques are used - traditional and transepithelial corneal crosslinking.

Conventional cross-linking

The operation is divided into 2 stages.

Stage 1: anesthesia Is performed, the spatula deepithelization of the cornea is carried out, and then the solution of Riboflavin is instilled for 25-30 minutes. After that, the doctor using a slit lamp assesses the degree of impregnation of the cornea drug. If the impregnation is sufficient, proceed to stage 2, if not-continue to instill until the desired result.

Stage 2 is to use a beam of ultraviolet light that interacts with Riboflavin, causing crosslinking of corneal collagen. This process also lasts about 30 minutes.

At the end of the operation, the antibiotic and anti-inflammatory drug are instilled, after which the patient is put on a soft therapeutic contact lens.

Transepithelial corneal collagen cross-linking (TE-CXL)

When using this technology, the removal of the top layer of the cornea is not required. He razryhlenija and becomes permeable to Riboflavin using spetsialnogo of the drug (tetracaine). In this regard, the patient is much less pronounced discomfort after surgery, much shorter rehabilitation period and less risk of various complications.

Corneal collagen crosslinking in keratoconus transepithelial costs and clinics

Possible cross-linking complications

For a long time, the complications of cross-linking were not mentioned in the professional literature. For the first time reports covering this topic appeared at the last ESCRS Congress. In our practice of cross-linking we also meet with typical complications:

  1. Varying degrees of severity of turbidity of the cornea. The quality of vision is usually not affected, but can be quite pronounced. Most often resorption occurs within 1-6 months, although it happens that this process takes up to 2 years.
  2. Eye irritation (1-2 weeks after surgery).
  3. Delay in re-epithelialization.
  4. Deterioration of the original visual acuity and its gradual recovery. This complication occurs rarely, vision is restored within 1-12 months.
  5. Melting of the cornea.
  6. Reactivation of herpetic infection, development of herpetic keratitis.

It should be noted that with all these complications, as a rule, it is possible to cope, and the use of transepithelial technology minimizes risks.

Video of the surgery of crosslinking in keratoconus

Results after crosslinking

It should be understood that since cross-linking has been practiced since 2004, full information about all the results, as well as about all the complications, is still unknown. But some conclusions are possible to do already now, in particular with regard to the application of crosslinking in keratoconus. With this method, it is possible to stop the development of the disease – this is the main result. There are no data on the progression of keratoconus after cross-linking surgery to date.

After surgery, 25% of patients have improved visual acuity by 1-2 lines-this is a consequence of the flattening of the cornea. Since the main task facing cross-linking with keratoconus is to stop the development of the pathological process, the effect of improving visual acuity is a pleasant "bonus". It is not yet clear why some patients have it, while others do not, so it is impossible to plan. In addition to this effect, 30% of patients improve the fit of hard contact lenses, which is made possible due to the same flattening of the cornea.

The price of cross-linking (CXL)

The cost of surgery in our specialized ophthalmological center is 34 000 rubles (530$) with the traditional method. With the technology of transepithelial cross-linking, the drug is additionally paid (about 5,000 rubles - 80$).

Feedback from patients after surgery

Below in the comments you can find other reviews of people who have already passed the procedure of corneal cross-linking or leave your own opinion.

# Michael 2015-10-22 06:25
Not everything is as terrible as it might seem - epithelium tear off, fact.
Then discomfort during the day, the lenses of course help, but not at all.
Well, then it grows rapidly...
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# Sara 2016-01-21 13:03
Hello please tell me the diagnosis keratoconus 3-4 stage/ thickness of the cornea at the clinic 480 nm, and in another clinic 360 nm, tell me how best to do that first segment and then cross-linking?
Some docs say the other segment from the CXL. Thank you in advance.
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# Consultant 2016-02-08 11:56
Dear Sara,
It all depends on the specific situation, there are various options for the treatment of keratoconus.
In the initial stages, usually, first held collagen crosslinking, then-implanted corneal segments (in the absence of effect).
In the developed stages of the disease, a simultaneous combination of methods is possible. It all depends on the specialist who leads you: what strategy he holds.

In any case, it is necessary to use both methods.
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# Amina 2017-03-27 19:20
Hi. I have been underwent crosslinking on one eye 4 days ago, before the operation was 0.2 now 0.1.
Explain this improvement or? and still a cloud over the eye. When will the turbidity pass?
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# Consultant 2017-03-29 08:14
Hello, Amina.

Reduced vision in the early postoperative period after crosslinking is a normal phenomenon, because the complete epithelization of the cornea and the cessation of inflammatory processes takes 1-2 weeks.

In some cases, low visual acuity may remain longer (if there are so-called" early stromal opacities"), but after 3 months after crosslinking visual acuity increases or returns to the preoperative level.
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# Nikolas 2017-04-11 09:50
And is it possible to decrease the thickness in six months after crosslinking and what is the reason?
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# Consultant 2017-04-11 10:55
Dear Nicolas
Reducing the thickness of the cornea after the procedure of crosslinking with Riboflavin is quite normal. This is due to the so-called "tightening effect" (or "compaction") resulting from the operation + the corneal oedema, which make the cornea more thick, is decreased.
Despite the decrease in thickness, the biomechanical properties improve and the progression of keratoconus slows down.
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# Angel95 2017-06-14 06:38
Hello, I have an operation of crosslinking, but the fact that I breastfeed, I was told that the operation can be done, then close the tear duct just when the drops to bury. It is possible to carry out so surgery, whether it is dangerous for the child?
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# Consultant 2017-06-14 07:44
Indeed, after the operation of crosslinking (especially the "traditional" method - with the removal of the epithelium), after the procedure, it is necessary for some time (up to a week) to instill antibacterial drops, which when ingested into the bloodstream (including being absorbed in the lacrimal tract) can be released with milk when feeding.

To avoid harm to the child, you can reduce absorption by closing the lacrimal points (as recommended) to refuse during rehabilitation from breastfeeding (decant, use the mixture), as well as to use the method of transepithelial corneal crosslinking (without removing the epithelium), the rehabilitation period is much less, because it is not necessary to remove the corneal epithelium.
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# Andrew 2017-11-24 13:39
Hi. The crosslinking of the right eye "2 degree" has been done 14. 11.2017
The question about improving vision... Will recover it's vision and for what period of time ?. So far all as it was, the image is blurred bifurcates
Thanks .
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# Consultant 2017-11-24 13:46
Dear Andrew,
You should understand that corneal cross-linking is performed not to improve vision (though such cases are), and for the strengthening of the cornea (the prevention of the progression of keratoconus).

To improve visual function, we recommend implantation of corneal ring segments (ICRS) and do it better before cross-linking.
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# Drago 2017-12-07 08:34
Hello, diagnosis-keratoconus 2 stage, could you tell me how to start treatment - with a hard lens, ICRS or crosslinking ? Thanks.
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# Consultant 2017-12-07 08:46
Dear Drago,
Scleral lenses is not a treatment, it is only a way of vision correction in keratoconus.

We recommend our patients to first to implant intrastromal corneal segments (ICRS) - in the "soft cornea", then - to do cross-linking (for its "strengthening"). But if the order of crosslinking and ICRS implantation is the opposite-there are no difficulties.
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# Zlotan 2017-12-17 16:37
Good day!
Three days ago I had a crosslinking on the left eye (keratoconus 3 St), photophobia is completely gone, the eye is wide open, no pain or discomfort is not present, but began to worry because the eye I see how to be through the muddy glass. Please tell me when it will gone?
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# Consultant 2017-12-18 08:27
Dear Zlotan, 3 days is a fairly early period after surgery and such" blurring " is the norm (usually patients are warned).
If complaints do not pass within 5-7 days, then this is an occasion to appeal to an ophthalmologist, because it is necessary to exclude the development of possible inflammation.
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# Denis 2018-02-17 08:47
Good afternoon.
Your authoritative opinion is required.
Two different doctors offer different sequence of alternation and intervals of procedures: Crosslinking and ring setting, both of which justify their position, but the rationale does not connect logically.
In what sequence in your opinion it is correct to work and with what interval?
CXL is offered to do on both eyes, ICRS is on one. I'm 33. The examination showed astigmatism and acuity-2 in the right eye and on it keratoconus 2 stage rolling in 3. The second eye keratoconus 1 stage and visual acuity -1.
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# Consultant 2018-02-17 11:40
Dennis, as stated above - no particular difference, but, typically, first perform the installation, intrastromal corneal segments, followed by the crosslinking.
Installation of ICRS is better to carry out with femtolaser support and with the use of author's nomograms (as we do in our clinic) - this gives a much better result in visual acuity than "manual installation without computer calculations" - which is offered to patients in most clinics.
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# George 2018-03-01 11:29
Hello I have keratoconus 4 stage vision -23
Can you do a crosslinking on my eyes?
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# Consultant 2018-03-01 11:38
When keratoconus stage 4 cross-linking is no longer effective (because the process is too far gone and the cornea is too thin). Here we can talk about DALIK or penetrating keratoplasty (PKP).
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# Dmitry 2018-03-10 16:25
Hi. Please tell me, what are the limitations after surgery, Crosslinking. Especially interesting at the expense of physical activity. If I train in the gym, when can I start training?
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# Consultant 2018-03-14 13:06
The restrictions apply to more "water sports" - swimming pools, baths, etc.It is better not to go there for at least 2 weeks.
If you just go to the gym, you can visit it in 2-3 days after the procedure (when the corneal epithelialization is finished) and the eyes will be comfortable.
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# psm62 2018-05-16 06:14
My Son in February has been underwent CXL -vision became worse than before the operation, was bad to see close (cloudy) on the eye there were two points.goes to the doctor every month , the doctor really can't answer how long will a course from which emerged these points. I am Very worried about this situation.
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# Consultant 2018-05-16 08:57
Hello Sir or Madam,
it is not clear what your question is, but comment on:
These complaints may be in the first few weeks after the corneal cross-linking procedure, but after 3 months everything should be normal.
As for the "points" - it is not clear where they are located - on the cornea, in float in the vitreous or other localization... In General, if your doctor finds it difficult to interpret the situation - we will be happy to answer all your questions and give recommendations after a intramural examination. Call us!
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# Alice 2018-06-06 20:31
Hello! I did 28.05.18 CXL in the right eye everything seems fine but the itchy eyes. Is this normal?
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# Consultant 2018-06-22 08:01
Dear Alice,
It is not clear when you started itching - if immediately after the procedure of cross- inking - it may be an allergic reaction - more often on drugs that are prescribed after surgery.
If the eye is scratched after some time, it may not be associated with cross-linking of the cornea, but be a separate symptom for the same Allergy, demodicosis, conjunctivitis, meibomitis, etc.
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# Poly 2018-06-26 17:59
Good evening. My boyfriend had a cross-linking yesterday and half a ring inserted. Please tell me how long the rehabilitation period will last, how soon the vision will be restored?
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# Consultant 2018-06-28 14:31
Hello, Poly.
The rehabilitation period after the corneal cross-linking procedure takes up to 1 month (during this period it is necessary to instill drops).
As for the improvement of vision - it begins to get better, almost from the first day and finally stabilized, usually within a month.
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