​​​​collagen corneal cross linking

Collagen Corneal Cross Linking is the latest hope for patients suffering keratoconus eye disease. 

Who invented Collagen Corneal Cross Linking?

Drs. G Wollensak and Seiler are credited with discovering cornea cross linking with riboflavin.

When and where  was  Collagen Corneal Cross Linking invented?

Dresden Germany at the turn of the century


BCVA:Best-corrected visual acuity

CXL: Corneal crosslinking

D: Diopter

DALK: Deep anterior lamellar keratoplasty

ICRS: Intracorneal ring segments

PRK: Photorefractive keratectomy 

SE:Spherical equivalent

UVA: Ultraviolet A irradiation

UCVA: Uncorrected visual acuity

Basic principles of Collagen corneal crosslinking

Main aim of corneal crosslinking: Halt increase in bulging of cornea. To make the cornea stronger and resistant to pressure of the eye.

Secondary Aim: Flatten the cornea and improve the vision.


Main actors are Riboflavin(Vitamin B2) and ultraviolet A irradiation (UVA). Riboflavin is the photosensitizer in the photopolymerization chemical reaction.  UVA irradiation excites free radicals, to form intrafibrillar and interfibrillar carbonyl-based collagen covalent bonds.

There are two phases of the process an early aerobic phase and later anaerobic. In the oxygen dependent aerobic phase molecules of riboflavin are excited to a single or triplet state. Reactive free oxygen radicals are liberated. These interact with collagen in the later anaerobic phase, when oxygen is depleted. As a result of this murky process corneal rigidity is increased,  collagen fiber become thicker and more resistant to enzymatic degradation. There is decreased permeability and swelling of the cornea especially in the anterior stroma.

Basic research results

Even with our modern technology it is difficult to demonstrate the exact working and the effect of cross linking on human cornea. We do have indirect evidence of the success of cxl. .Youngs modulus or stress strain ratio is increased with c3r and is the hallmark to demonstrate the effectiveness in the lab.The strengthening is more if higher content of collagen is present . In porcine cornea cross linked cornea are more resistant to swelling.

Both humans and rabbit cornea develop more collagen fibers thickness after C3R.  CXLtreatment makes the cornea  more resistant  to degradation processes mediated by pepsin, trypsin and collagenase with increase in collagen turnaround time.

Indications for collagen corneal cross linking

  1. Progrssive Keratoconus
  2. Lasik ectasia getting worse
  3. Pellucid Marginal Degeneration which is deteoriating

An important fact we have to consider is what we mean by progression. Various researchers, clinicians and surgeons may define it differently. It may also vary by the machines used for topography or OCT. A pentacam may show numbers differently than an Atlas topography. Therefore the surgeons experience becomes important. It may be be better to err on the side of caution.

We also need to come up with a standard for defining progression among Keratoconus doctors.  Progression in various studies is considered

  1. When there is an increase Kmax of 1 diopter (D) in 1 year
  2. Increase in nearsightedness and/or astigmatism ≥3 D in 6 months,
  3. A mean central K-reading change ≥1.5 D observed in three consecutive topographies in 6 months,
  4. If there is a decrease ≥5 % in mean central corneal thickness in three consecutive tomographies in the last 6 months.

Contraindications to undergoing standard CXL treatment

  1. Corneal thickness of less than 400 microns
  2. Previous herpetic infection
  3. Immunological disease
  4. Severe scarring or haziness of cornea.
  5. Epithelial wound healing problems
  6. Severe dry eye or surface disorders
  7. Finally  pregnancy and breast-feeding 

Standard procedure and clinical results of collagen corneal cross linking

The standard Dresden protocol, also called conventional collagen corneal cross linking was described by Wollensask. It requires epithelial removal, the instillation of 0.1 % riboflavin solution for 30 min followed by 30 min of UVA irradiation with a wavelength of 370 nm and power of 3 mW/cm2 (5.4 J/cm2).



Keratoconus fighter


Finding a passionate, caring Keratoconus Surgeon with great bedside manners was fortunate. The results have been more than I anticipated. Thankyou Dr.Khanna.

The great news is that research papers with followups ranging from 6 months to 6 years, all showed stabilization of keratoconus with flattening of central cornea. There was also documentation of improvement of vision with epic off collagen corneal cross linking.


Limits and complications of collagen corneal cross linking

  1. In around 8.1–33.3 % of patients cxl may not be beneficial. The central cornea continues to steeped more than 1 D in a year, or vision deteriorates further.
  2. Infection remains the main problem. Bacteria, fungus, herpes and acantamoeba can all invade the denuded cornea. Clinicians and patient have to be vigilant against this threat.
  3. Corneal haze is quite common. It occurs three weeks to three months later. the good news is that it resolves on its own. It may be relates to keratocyte activation
  4. Corneal edema may occur
  5. Watering, tearing, pain are frequent benign.

If you are looking for help with halting the progression of your Keratoconus, look no further. Our Los Angeles Keratoconus

Experts are here to help. Write or call us to set up appointment for a personalized approach to your eye.


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