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  Corneal Collagen Crosslinking C3R with riboflavinn Dr  Hijab  Mehta 2010-10-04 06:57:34  
Keratoconus is a noninflammatory cone like ectasia of the cornea, which is usually bilateral and progresses over time. Its reported frequency is approximately 1 in 2,000 in the general population. Usually, the condition starts at puberty, progressing in approximately 20% to such an extent that a lamellar or penetrating keratoplasty becomes necessaryy

Besides keratoplasty, rigid gas permeable contact lenses are the major treatment modality for keratoconus. Intracorneal rings or Intacs is the other procedures which could be considered. However, all of these techniques only correct the refractive errors of keratoconus but do not treat the cause underlying the corneal ectasia and therefore cannot stop the progression of keratoconus.

A new technique of collagen cross linking by the photosensitzer riboflavin and UVA similar to photopolymerization in polymers has been developed. Popularly known as Corneal Collagen Cross linking (C3-R) with Riboflavin (Vitamin B2), this new treatment is aimed at the pathogenic cause of keratoconus and changes the intrinsic biomechanical properties of corneal collagen.

What is this?

Cross linking is a widespread method in the polymer industry to harden materials and also in bioengineering to stabilize tissue. For example, chemical cross linking with glutaraldehyde is used in the preparation of prosthetic heart valves and physical cross linking with UVA is used in Dentistry to harden filling material.

UVA irradiation in combination with Riboflavin initiates molecular cross linking of corneal collagen that is, creation of new bridges among collagen fibers. This increases the biomechanical strength of the corneal tissue and can arrest, progressive corneal thinning and Ectasia

Clinical Studies with five years follow up post C3R have demonstrated a stabilization of Keratoconus with no further progression. Also a flattening of the keratometry by two diopters and an improvement in the best corrected visual acuity by 1.4 lines has been reported.

How does this work?

After instillation of photosensitiser riboflavin, the cornea is exposed to UVA light at 370nm; a wavelength that corresponds to one of the absorption maxima of the riboflavin chromophore, the photosensitiser is excited into generating Reactive Oxygen Species (ROS). The ROS react with various molecules inducing formation of chemical covalent bonds between collagen fibrils known as cross linking.

Studies have showed a significant increase in corneal rigidity by approximately 70% in untreated vs. treated corneas after collagen cross linking by the combined riboflavin/UVA treatment.


Progressive Keratoconus

Iatrogenic Corneal Ectasia

Pellucid Marginal Corneal degeneration


Corneal thickness of 400 microns and above

Risk and side Effects

UV light in general has potential harmful effects on the human eye. We know of UV induced photochemical damage sunburn or photokeratitis, both of which are caused, however, by UVB-light. In the Cornea UVB-light (290-320nm) is mainly absorbed by the corneal epithelium as can be seen in snow blindness. In cross linking treatment the UVA-spectrum (370nm) is used, and during the treatment UVA absorption is massively increased in the cornea due to presence of photosensitiser riboflavin, resulting in UVA transmission across the Cornea of only 7%.

The treatment effect of cross linking is localized to the anterior 300 microns of corneal stroma. Using the current recommended treatment parameters and restricting the procedure to corneas with a pachymetry of 400 microns and above, avoids damage to the endothelium, lens and retina.

There is good reason for the hope that the cross linking treatment will be a breakthrough in the management of keratoconus reducing significantly the need for Cornea transplantation.


1.Spoerl E, Mrochen M, Sliney D, Trokel S, Seiler T.Safety of UVA-riboflavin cross-linking of the cornea. Cornea. 2007 May; 26(4):385-9. 2. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus.Am J Ophthalmol. 2003 May; 135(5):620-7. 3. Wollensak G. Crosslinking treatment of progressive keratoconus: new hope.Curr Opin Ophthalmol. 2006 Aug; 17(4):356-60. 4. Mazzotta C, Traversi C, Baiocchi S, Sergio P, Caporossi T, Caporossi A.Conservative treatment of keratoconus by riboflavin-uva-induced cross-linking of corneal collagen: qualitative investigation. Eur J Ophthalmol. 2006 Jul-Aug; 16(4):530-5. 5. Caporossi A, Baiocchi S, Mazzotta C, Traversi C, Caporossi T. Parasurgical therapy for keratoconus by riboflavin-ultraviolet type A rays induced cross-linking of corneal collagen: preliminary refractive results in an Italian study. J Cataract Refract Surg. 2006 May; 32(5):837-45.

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