Corneal collagen cross-linking significantly improved keratometry and
visual acuity 1 year after treatment in patients with keratoconus and corneal
ectasia, a study found.
The goal of the study was to determine the efficacy of corneal collagen
cross-linking in slowing the progression of keratoconus and ectasia after
“Cross-linking, which is still an investigational procedure …
would give ophthalmologists their first therapy for decreasing keratoconus
progression,” lead study author Peter S. Hersh, MD, FACS, told
Ocular Surgery News.
Cross-linking creates additional bonds between collagen molecules, which
cause the cornea to stiffen. Dr. Hersh said the treatment could be
groundbreaking in the management of keratoconus.
Study results were published in Journal of Cataract and Refractive
Researchers evaluated 71 eyes of 58 patients who underwent standard
corneal collagen cross-linking with ultraviolet A light and topical riboflavin
0.1%. Patients with corneas thinner than 400 µm also received hypotonic
riboflavin 0.1% drops until the cornea was of adequate thickness.
Of the eyes included in the study, 49 had keratoconus and 22 had corneal
ectasia. Researchers conducted follow-up examinations at 1, 3, 6 and 12 months
The prospective, randomized, controlled clinical trial included a sham
control group in addition to a fellow-eye control group.
The sham control group included 41 eyes that received riboflavin 0.1%
alone and were followed for 3 months postoperatively. Dr. Hersh said patients
with potentially treatable keratoconus underwent full cross-linking at 3 months
due to ethical considerations and noted that the short-term follow-up period
was a limitation of this group. Therefore, 30 eyes in a fellow-eye control
group that did not receive any treatment were evaluated for comparison to
treated eyes as well. Although these eyes completed the 12-month follow-up
period, Dr. Hersh said that the comparative results were limited because the
group was not randomized and the severity of keratoconus varied.
Patients were analyzed as a cohort and then individually within
keratoconus or ectasia subgroups.
Changes in uncorrected distance visual acuity, corrected distance visual
acuity, maximum keratometry value and average keratometry value from baseline
to 3 months were not significantly different between the treatment group and
the sham control group at 3 months, the study said.
All groups, however, showed significant improvements in mean uncorrected
distance visual acuity (P = .04) and corrected distance visual acuity
(P < .001)="" 1="" year="" after="" treatment.="" the="" entire="" cohort="" experienced="" the="" most="" improvement="" between="" baseline="" and="" 3="" months="" and="" 3="" months="" and="" 6="" months,="" and="" researchers="" observed="" a="" plateau="" in="" improvement="" and="" stabilization="" for="" the="" remainder="" of="" the="" study.="">
According to Dr. Hersh, the healing process can take months to complete
and is marked by periods of improvement, stabilization and sometimes early
worsening of certain measures.
“The stabilization and improvement we are seeing in corneal
steepness and distance corrected visual acuity represents the complete course
of the actual cross-linking event and the subsequent wound healing that goes on
afterward,” he said.
Maximum keratometry was considered the primary outcome because it gives
some indication of the severity of the keratoconic cone, according to the
After 1 month, all groups showed a significant increase in maximum
keratometry value, followed by significant decreases between 1 month and 3
months and 3 months and 6 months. No significant change was observed between 6
months and 12 months, which follows the same stabilization curve as the other
measures, Dr. Hersh said.
At 12 months, the treatment group showed significant improvements in all
outcome measures compared with the fellow-eye control group. On average,
maximum keratometry flattened by 1.7 D, uncorrected visual acuity improved from
20/137 to 20/117, and corrected distance visual acuity improved from 20/45 to
20/34. The researchers are currently analyzing changes in topography indices
and wavefront measurements after cross-linking in this patient group.
Dr. Hersh and colleagues are conducting a number of studies to further
evaluate the parameters of corneal collagen cross-linking. One trial aims to
determine whether cross-linking and implanting Intacs (Addition Technology)
should be done together or separately with a 3-month healing period in between.
Another study is evaluating the use of hypotonic riboflavin vs. the
standard dextran formulation to determine whether hypotonic riboflavin provides
a more consistent corneal thickness throughout the cross-linking procedure. Dr.
Hersh said he hopes to present the results of both studies soon.
The researchers are also conducting a multivariate analysis that will
determine the most appropriate and inappropriate candidates for corneal
collagen cross-linking. They are looking for characteristics that could predict
a stable or improved result, and preliminary results suggest that patients with
higher keratometry readings, steeper cones and worse best corrected visual
acuity may benefit more from the procedure. Final results are due later this
spring, he said.
Dr. Hersh said that the research will look at other indicators of
success or failure as well in order to determine the best candidates for
cross-linking. – by Courtney Preston
- Hersh PS, Greenstein SA, Fry KL. Corneal collagen crosslinking for
keratoconus and corneal ectasia: one-year results. J Cataract Refract
- Peter S. Hersh, MD, FACS, can be reached at The Cornea and Laser
Eye Institute, 300 Frank W. Burr Blvd., Suite 71, Teaneck, NJ 07666;
201-883-0505; fax: 201-692-9646; email:
- Disclosure: Dr. Hersh is medical monitor to Avedro Inc.
Riboflavin UV cross-linking was first described by Seiler more than a
decade ago. Since then, multiple studies have demonstrated its safety and
efficacy in preventing the progression of keratoconus, but less is known about
the role of this technology in the management of ectasia after refractive
surgery. Hersh and colleagues have further corroborated the efficacy of
riboflavin UV cross-linking in the treatment of keratoconus. Their findings
showed improvements in uncorrected and best corrected visual acuity in the
treated patients and continued worsening in the untreated control group. In
addition, treated patients had a decrease in maximum and mean keratometry
values. The results in the post-refractive ectasia group were also significant,
but not as robust as in the keratoconus group. This study further documents the
importance of riboflavin UV cross-linking, as well as the necessity of this
technology to become routinely available in the United States.
– Eric D. Donnenfeld, MD
Cornea/External Disease Board Member
Disclosure: Dr. Donnenfeld has no
relevant financial disclosures.