Collagen Cross-Linking (CCL) using Riboflavin and UV (365nm) exposure or C3R
Keratoconus is a disorder of the cornea characterized by progressive thinning and ectasia which results in
deterioration of the quality of vision and also the quality of life. As the disease begins in young adults, it affects
the most productive years of life. So far there has been no effective way to stop the progression of keratoconus.
Current methods such as rigid contact lens, & intracorneal ring segments only the refractive error can be
corrected without any effect on the progression of keratoconus. It is estimated that eventually 21% of the
keratoconus patients require surgical intervention to restore corneal anatomy and eyesight.
A new modality of treatment, based on collagen crosslinking with the help of Ultraviolet A (UVA, 365nm) and the
photosensitizer riboflavin phosphate has been described which changes the intrinsic biomechanical properties of
the cornea, increasing its strength by almost 300%. This increase in corneal strength has shown to arrest the
progression of keratoconus in numerous studies all over the world.
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Collagen Crosslinking treatment

Eligibility Criteria

- Patients with progressive Keratoconus
- Minimum corneal thickness of 400 microns
- Maximal keratometry readings < 60 D
- No other corneal disease
- Patients over the age of 16 years
Current Corneal Collagen Crosslinking with Riboflavin Medical Journal News...

Crosslinking treatment of progressive keratoconus: new hope.
Curr Opin Ophthalmol. 2006 Aug;17(4):356-60
Authors: Wollensak G

PURPOSE OF REVIEW: A new method has been introduced for the treatment of progressive keratoconus using
collagen crosslinking by the photosensitzer riboflavin and ultraviolet A-light. Biomechanical measurements have
shown an impressive increase in corneal rigidity of 328.9% in human corneas after crosslinking. RECENT FINDINGS:
The 3 and 5-year results of the Dresden clinical study have shown that in all treated 60 eyes the progression of
keratoconus was at least stopped ('freezing'). In 31 eyes there also was a slight reversal and flattening of the
keratoconus by up to 2.87 diopters. Best corrected visual acuity improved slightly by 1.4 lines. So far, over 150
keratoconus patients have received crosslinking treatment in Dresden. Laboratory studies have revealed that the
maximum effect of the treatment is in the anterior 300 mum of the cornea. As for the corneal endothelium, a cytotoxic
level for endothelium was found to be 0.36 mW/cm which would be reached in human corneas with a stromal
thickness of less than 400 mum. SUMMARY: Collagen crosslinking by the photosensitzer riboflavin and ultraviolet
A-light is an effective means for stabilizing the cornea in keratoconus. Collagen crosslinking might become the
standard therapy for progressive keratoconus in the future diminishing significantly the need for corneal
transplantation. Preoperative pachymetry and individual control of the ultraviolet A-irradiance before each treatment
are mandatory. The treatment parameters must not be varied.

PMID: 16900027 [PubMed - indexed for MEDLINE]

What is collagen cross-linking?
Collagen cross-linking is a new treatment for keratoconus, that uses a photosensitizing agent, riboflavin (vitamin B2)
& ultraviolet light (UVA, 365nm) exposure. In extensive experimental studies (including biomechanical stress & strain
measurements) researchers have demonstrated a significant increase in corneal rigidity / stiffness after collagen
cross-linking using this riboflavin/UVA treatment. The 3 & 5 year results of Dresden clinical study in human eyes has
shown arrest of progression of keratoconus in all treated eyes.  (Wollensak G. Crosslinking treatment of progressive
keratoconus: New Hope. Current Opinion in Ophthalmology 2006; 17: 356 – 360)

How is the treatment done?
The treatment is performed under topical anesthesia. The skin (epithelium) of the surface of the cornea is partially
scratched, followed by application of Riboflavin eye drops for 30 minutes. The eye is then exposed to UVA light for 30
minutes. After the treatment, antibiotic ointment is applied and an eye-pad is worn overnight until the next day when
the surface of the eye has healed. Oral analgesics are required for the first 1 -2 days

Who can benefit from this treatment?
Collagen cross-linking treatment is not a cure for keratoconus, Rather, it aims to  halt the progression of the
condition. This is important to understand. Patients will continue to wear spectacles or contact lenses (although a
change in the prescription may be required) following the cross-linking treatment. The main aim of this treatment is to
arrest progression of keratoconus, and thereby prevent further deterioration in vision and the need for corneal
transplantation. However in advanced keratoconus, wherein the corneal thickness is below 350 microns, this
treatment may not be possible. In such a situation other alternatives such as deep anterior lamellar keratoplasty
(DALK) should be considered.
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Dr Rajesh Fogla, senior corneal surgeon has special interest in keratoconus disorder and its management. He has a vast experience in contact lens fitting, &
specialized corneal procedures to effectively manage this condition.
He has been performing Deep Anterior Lamellar Keratoplasty since 1998, & has numerous publications & presentations on the same

For more information regarding the cost of surgery and other details you can email Dr Rajesh Fogla at or call him on +91 9866076750
Cornea Clinic
Cornea Clinic - Eye Department - Apollo Hospitals, Jubilee Hills, Hyderabad 500 033, A P,  INDIA
Cornea Clinic - toll free number 1600 345 1066, other numbers 91 40 23608333 / 23548888 / 23606655
Tel 91 40 23607777,  Fax 91 40 23608050 ,24 hours emergency services call 1066
Click here to take a look at
clinical outcome of collagen
crosslinking treatment