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CXL Crosslinking – Advanced Treatment Procedure for Keratoconus

CXL – an advanced treatment procedure for Keratoconus

Keratoconus is an eye condition in which a person suffers from serious vision abnormalities due to deformity of the corneal structure. The cornea normally has a round structure which helps in focusing the light appropriately to the retina (usually called the screen of the human eye). But, in a keratoconic patient, the round shape of the cornea becomes conical, which leads to vision impairment.

It is a progressive disorder which aggravates with time and causes frequent prescription changes.  Though there is no permanent cure for the disease till date, available treatment options other than CXL are effective in restoring the vision of the patient up to a limited extent. With advancement in technologies, research and knowledge, an advanced procedure known as Corneal Cross Linking (CXL) to deal with keratoconus emerged.


The emergence Corneal Cross linking

Keratoconus is a progressive disorder and before the advent of CXL, no other treatment option was capable of halting its progression along with treating the refractive errors associated with the disease. Corneal Cross Linking also known as Corneal Collagen Cross Linking is a new but an advanced and well established treatment alternative which is highly effective to deal with keratoconus progression. During CXL, new chemical bonds between collagen fibres are formed and the corneal resistance towards enzymatic degradation increases. This halts the progression of keratoconus in the CXL treated patients and thus corneal transplant is never required. In addition to treating keratoconus, CXL is also opted for the treatment of post-LASIK ectasia, and pellucid marginal degeneration.

The first use of CXL procedure for treating keratoconus was done in the year of 1998 in the Department of Ophthalmology at Technical University of Dresden, Germany. The results thus far suggested CXL to be a very effective procedure for halting the progression of the disease. Recently (on 18th April, 2016), FDA has approved the Riboflavin Ophthalmic Solution/KXL™ System of the Avedro, Inc for the treatment of progressive keratoconus after years of clinical trials.


CXL Procedure and variants

The culprit behind the change in the structure of cornea is the weakening of collagen fibres. Collagen fibres are the thread like proteins which act as a meshwork for building the structure of the cornea. When this fibrous meshwork or network becomes week, it loses the ability to hold the cornea in its original shape and structure. So, the CXL procedure targets on strengthening of the meshwork for keeping the corneal structure intact thus prevent its conical bulging.

CXL is an outpatient procedure and is usually completed in 1-2 hrs. In this process, collagen, the fibrous protein which gives cornea its rigid structure, is strengthened by cross linking with the help of riboflavin and ultra violet light. There are two methods of performing CXL:

Epithelium-Off CXL and Epithelium-On CXL procedures

The epithelium is the outermost layer on the front surface of the cornea. It acts as a barrier and protects the cornea from the entry of harmful things like bacteria and also prevents the free movement of fluids out from the cornea.

  1. Epithelium off CXL:

Epithelium-off CXL is the standard procedure followed in most of the patients. The first step of the procedure involves removal of the epithelial layer of the cornea. Riboflavin eye drops are then instilled into the affected eye and kept undisturbed for up to 30 minutes to let the riboflavin absorbed by the corneal tissue. The corneal tissue is then irradiated by UV radiation (at 365 nm) for 30 minutes.

  1. Epithelium-On CXL or Accelerated cross linking

In epithelial-on CXL also known as accelerated cross linking or trans-epithelial CXL, the epithelial layer of the cornea is kept intact and undisturbed while riboflavin drops are instilled into the cornea. To facilitate the penetration of riboflavin, substances like benzalkonium chloride are added to riboflavin solution.  In addition to being a common preservative for eye drops, benzalkonium chloride is an active agent that changes the surface tension of the epithelial layer of cornea thus, enhances the penetration of riboflavin. 30 minutes after instillation of riboflavin the cornea is exposed to ultraviolet radiation (at 365 nm).

The whole CXL procedure is completed in about one hour for one eye. The surgeon will administer a combination of topical steroid and antibiotic eye drops (like moxifloxacin eye drops 0.5%, prednisolone acetate 1% eye drops) after the treatment which could be followed by applying bandage contact lens (in case of epi-off procedure). The bandage contact lens if used will be removed during the follow up visit.  It might be suggested to use protective sunglasses for a few days after the treatment till the patient’s eye completely heals.


Choosing the right type of CXL procedure

Before performing the CXL the surgeon will verify various things to choose the type of procedure that best suits the specific needs of the patient. One major factor which is considered for determining the type of CXL procedure is the thickness of the cornea. Epi-on CXL is usually considered in instances where patient’s cornea is not thick enough for the standard epi-off procedure.

The role of riboflavin and UV rays

Riboflavin, also known as vitamin B2 is a biological component which is normally required by human body to perform various important roles like in that in fats and carbohydrate digestion. Thus it is an essential component of a well balanced diet. In CXL procedure, riboflavin with UV light plays two roles:

  1. Formation of free radicals

Riboflavin produces the free radicals or the reactive oxygen species in the UV exposed corneal tissue by a process known as photosensitization. These free radicals induce the formation of new covalent bonds between the collagen fibres in the corneal meshwork thus results in strengthening of the cornea.

  1. Shielding effect

Riboflavin also absorbs UV light thus; it prevents the potential damage of the internal parts of the eye like lens or retina which can occur due to UV exposure. This is the reason behind 30 minutes gap between riboflavin instillation and UV exposure. The riboflavin absorbs about 95% of the UV radiation at wavelength 390 nm.


Post CXL care

The patient must follow the precautions as suggested by the doctor. Use of the prescribed eye drops regularly as suggested is important. The patient can carry day-to- day activities after a day or two but it is recommended to take at least one week off from job.  If the job of the patient involves extensive use of computers, it will be recommended to take off for at least about two weeks. The patient can wash or shower normally but putting water in eyes should be avoided.  Follow-up as prescribed by the surgeon is a must.


Benefits of CXL over other treatment options:

  1. Permanent treatment
  2. As CXL treats the underlying issue of the disease, the patient never requires corneal transplant
  3. CXL is completely safe and highly effective procedure. The procedure is also FDA approved now
  4. Simple one-time treatment with no need for injections or stitches
  5. The procedure stops the progression of the disease thus, the disease will not aggravate with time.
  6. Freedom from frequent glass prescription changes
  7. Fast recovery with short follow up


The right candidate for CXL                        

Any keratoconus patient who is diagnosed with progression of the disease for about 12 months or more under the age of 40 years will be an ideal candidate for Collagen corneal cross linking procedure.

In terms of vision deformities, the patient should be having an increase of at least 1 dioptre in case of astigmatism, and a myopic shift with minimum 0.5 dioptres in terms of steepest keratometry readings.

Keratoconus progression is at peak in younger patients while the disease stabilizes after the age of 40 years. Thus, it is suggested that the patient should opt CXL as early as possible and is usually not needed after the age of 40 years. The minimum age of the patient to undergo CXL procedure is 12 years.


Concern of using UV light

It is well known that ultra violet light is harmful to humans and can cause potential damage to vital layer of cornea, retina or lens if used directly on the eyes. The use of ultra violet rays during CXL procedure thus presents a reason for concern in patients. But the CXL procedure is actually a very SAFE and EFFECTIVE procedure.

There are two things to understand to ease the concern of UV light use in CXL. First, the wavelength of UV light that is used in CXL i.e., 365 nm, is completely safe for use.  Secondly, the riboflavin used during the procedure absorbs about more than 95% of the used UV radiation thus preventing the penetration of the UV light to internal parts of the eye. Thus, the potential side effects of UV light are eliminated.