Collagen cross-linking one possibility to treat ectasia and keratoconus

Experimental approach with riboflavin tested by some clinicians

Post-LASIK ectasia.
Source: Amar Agarwal, M.D.

Collagen cross-linking with riboflavin may be one way to treat iatrogenic ectasia, said Amar Agarwal, M.S., F.R.C.S., Dr. Agarwal's Eye Hospital, Chennai, India.
The technique uses ultraviolet A (UVA) light and riboflavin to create new bonds between the adjacent collagen molecules so that the cornea is one and a half times thicker and less malleable, he said.
The approach was discussed at a course on refractive surgery worst case scenarios at the 2006 ASCRS•ASOA Symposium & Congress.

Ectasia and collagen crosslinking

Ectasia can occur when ablation is too severe, Dr. Agarwal said. “The posterior surface of the cornea starts bulging immediately” when someone has iatrogenic ectasia, he said. The patient may have difficulty reading, and the consequences can become more severe if the ectasia is not treated quickly, Dr. Agarwal said.
Traditionally, ectasia is treated with special contact lenses or deep anterior lamellar keratoplasty, Dr. Agarwal said. Reverse-geometry rigid gas permeable lenses, the Boston scleral lens (invented by Perry Rosenthal, M.D., Boston Foundation for Sight, Needham, Mass.), and the Eni-Eye (AccuLens, Denver) are options that other clinicians have used for ectasia treatment. However, Dr. Agarwal said he finds the experimental approach of collagen cross-linking with riboflavin promising. Also known as C3-R, it is used to treat ectasia and keratoconus.
“It is, in essence, an exaggeration of the normal cross-linking that occurs with age and as a pathological process in diabetics,” Dr. Agarwal said. The treatment is not yet approved for commercialization in the United States, said Brian S. Boxer Wachler, M.D., Beverly Hills, Calif., who has studied C3-R.
C3-R is painless, non-invasive, and allows the patient to go home immediately after surgery, said Roberto Pinelli, M.D., Brescia, Italy. The procedure also makes corneal collagen tissue stronger and helps keratoconus patients avoid a corneal transplant, he said.

The technique and study results

The C3-R treatment involves removal of a 7-mm to 9-mm area of the epithelium and application of 20% riboflavin in dextrane solution on the cornea, Dr. Agarwal said. Irradiation of the cornea with the UVA light then occurs. The light is 1 cm away from the patient and is used for 30 minutes. It is a one-time procedure.
“These settings have been found to be safe for the endothelium as well as with pachymetry of at least 400 microns,” he said. After the procedure pachymetry in eyes with at least 400 microns usually indicates a thickening of the cornea by about 20 to 30 microns, Dr. Pinelli said.
In other studies Dr. Agarwal reviewed on the topic the ectasia improved in about 50% of cases, as did best-corrected visual acuity and maximal keratometry values.
Dr. Pinelli also has seen positive outcomes and high patient satisfaction in a prospective, non-randomized, single-center trial using C3-R treatment for keratoconus. The three-month results from 10 eyes are promising, he said.
“Preliminary results of the study show that C3-riboflavin is an interesting option for improving visual ability of patients affected by keratoconus and other ectatic disorders,” he said.
However, patients should know in advance that improvement of their uncorrected visual acuity (UCVA) does not always occur.
“The goal of the technique is to stop the progression of the keratoconus or of the corneal ectasia, not to improve patients' UCVA, although the refractive aspect of the procedure is very important,” Dr. Pinelli said.
In Dr. Boxer Wachler's work with 27 eyes of 23 patients, C3-R was safe, stabilized or even reversed corneal steepening, and was enhanced by the use of inferior segment Intacs (Addition Technology, Des Plaines, Ill.), he said.
Dr. Boxer Wachler and Colin C.K. Chan, M.D., Australia, compared the results from 12 eyes of nine patients treated with inferior segment Intacs but no C3-R treatment and 15 eyes of 14 patients that were treated with inferior segment Intacs followed by C3-R. The main aim of the study was to test the effectiveness of C3-R for keratoconus and keratoectasia.
Comparing pre-op results, one-day post-op results, and results measured at the last post-op visit, the group with the combined Intacs/C3-R treatment had a significantly greater reduction in cylinder than the group with only Intacs, Dr. Boxer Wachler said. The reduction was 2.52 D in the combined treatment group versus 1.48 D in the group with Intacs only. The K steep and K average were also reduced more significantly in the group with combined treatment, he said. Dr. Boxer Wachler presented these study results at the 2006 ASCRS•ASOA Symposium & Congress.
“The C3-R treatment can be performed before Intacs surgery because the corneal tissue is stronger, and the degenerating ectasia/keratoconus process is stopped. Then the effect of the Intacs is increased,” Dr. Pinelli said.
Refractive surgeons from around the world, including Drs. Pinelli and Boxer Wachler, are tracking the results from C3-R treatment with their patients and recently attended the First International Congress on Corneal Cross Linking, Dr. Pinelli said.

Editors' note: Drs. Agarwal and Pinelli do not have any financial interests related to their comments. Dr. Boxer Wachler is a consultant for Addition Technology and Alcon (Fort Worth, Texas).

Contact Information
Agarwal: +91-44-28116233, dragarwal@vsnl.net.in
Boxer Wachler: 310-860-1900, bbw@boxerwachler.com
Pinelli: +39-030-242-8343, pinelli@ilmo.it