Cornea
Cross-linking vision improvement evidence mounts

At a glance: Cross-linking • Corneal collagen crosslinking (CXL) stabilizes progression of keratoconus and significantly improves visual acuity while reducing aberration • CXL received CE mark in all 25 European countries as of 12/06

Study adds to the growing body of research that the emerging procedure of CXL can improve visual outcomes in progressive advanced keratoconus cases

Corneal riboflavin (stromal fluorescence) penetration through intact epithelium

Pre and one-year post C3-R showing stability and 1.70D of flattening Source for both: Brian S. Boxer Wachler, M.D.
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An emerging corneal treatment improved uncorrected and best spectacle corrected visual acuities in patients with progressive advanced keratoconus, according to the latest in a growing number of studies on the visual outcomes of the procedure.
Corneal collagen cross-linking with riboflavin (CXL), prevents the cornea from bulging out and becoming steep and irregular. It’s an emerging treatment for keratoconus, where practitioners previously have had very limited options—relying on use of rigid gas permeable contact lenses and more recently on use of Intacs (Addition Technology, Des Plaines, Ill.) to help alleviate visual problems.
Although some studies found a lack of visual improvement from the procedure, a growing body of recent research has found that not only did CXL stabilize progression but it resulted in “significant” improvements in visual acuity and reductions in aberrations.
One recent study found that two years post-op CXL appeared effective in improving uncorrected and best spectacle-corrected visual acuities (BSCVA) in eyes with progressive keratoconus by significantly reducing corneal average pupillary power, apical keratometry, and total corneal wavefront aberrations. “We conclude that the refractive outcomes were achieved by a flattening of the cone apex and a steepening of the part of the cornea symmetrically opposite the cone,” wrote Paolo Vinciguerra, M.D., Department of Ophthalmology, Istituto Clinico Humanitas, Milan, Italy, and colleagues. The study, titled “Intraoperative and Postoperative Effects of Corneal Collagen Cross-linking on Progressive Keratoconus,” was published in the October 2009 issue of the Archives of Ophthalmology.
The prospective, nonrandomized single-center clinical study of the procedure used in 28 eyes found that two years after treatment deterioration of the Klyce indices was observed in the untreated contralateral eyes but not in treated eyes. Although mean 12-month baseline pupil center pachymetry and total corneal volume decreased significantly, endothelial cell counts did not change significantly.
Similar visual acuity improvements stemming from the procedure were identified in 2001 and 2008 studies, noted Dr. Vinciguerra and colleagues. The improved post-op visual acuities were explained by “significant reductions” of simulated keratometry, average pupillary power, apical keratometry, apical gradient curvature, inferior-superior index, cone area, corneal aberrations, and the Klyce and Ambrosio indices, they wrote.
The findings are important because they point to the potential benefits of an emerging procedure to a once-untreatable condition.
The innovative approach received the CE Mark in all 25 European countries as of December 2006. And an ongoing FDA clinical trial is examining U.S. approval of the treatment.
Esen K. Akpek, M.D., associate professor of ophthalmology, and director, Ocular Surface Diseases and Dry Eye Clinic, Wilmer Eye Institute, Johns Hopkins University, Baltimore, was not surprised by the findings. “It is known that the procedure improves uncorrected and best spectacle corrected vision,” Dr. Akpek said.
However, she noted that the significance of the study results is limited by its two-year duration. Because long-term outcomes were not studied, the possibility of regression remains a concern. A 10-year study is needed to fully address lingering concerns about endothelial cell counts, whether a rebound of ectasia occurs and whether the results are stable, Dr. Akpek said.
An August 2009 study of 117 eyes undergoing CCL published in the Journal of Cataract and Refractive Surgery found one-year post-op 2.9% lost 2 or more Snellen lines, while 7.6% of eyes had continued progression. That study concluded that CXL inclusion criteria may significantly reduce the complications and failures, including a pre-op maximum K reading of less than 58.00 D and restricting patient age to younger than 35 years old.
Brian S. Boxer Wachler, M.D., director, Boxer Wachler Vision Institute, Los Angeles, said the study echoed his clinical experience with CXL over the last six years. However, Dr. Boxer Wachler noted that there are some differences in results that likely stem from the removal of the epithelium during standard CXL that results in a thinner corneal pachymetry, at least in the short term. Dr. Boxer Wachler uses intracorneal ring segments to cross-link with intact epithelium, which he calls C3-R, to avoid this. “With C3-R, there is no worsening before the cornea shape improves,” he said.
The findings of Dr. Vinciguerra and colleagues, said Dr. Boxer Wachler, show that the K values were steeper when the cornea was measured after epithelium was debrided and supports the notion that the epithelial acts as a “masking” agent in very early stage keratoconus. That belief stemmed from the work of Dan Reinstein, M.D., founder, London Clinic, London, who found that the epithelium is thinner in patients with keratoconus, even before keratoconus is evident on corneal topography.

Editors’ note: Drs. Akpek, Boxer Wachler, and Vinciguerra have no financial interests related to their comments.

Contact information

Akpek: 410-955-5494, esakpek@jhmi.edu
Boxer Wachler: 310-860-1900, bbw@boxerwachler.com
Vinciguerra: paolo.vinciguerra@humanitas.it