Corneal Cross-Linking in Children With Keratoconus Improves Visual Acuity

Kathleen Louden

November 01, 2010

November 1, 2010 (Chicago, Illinois) — Corneal collagen cross-linking appears to be safe and effective for children with progressive keratoconus, a new study from Italy has found. Results were presented here at the American Academy of Ophthalmology and Middle East Africa Council of Ophthalmology 2010 Joint Meeting.

"Keratoconus seems to progress [more rapidly] in young patients," said the presenting author, Elena Albé, MD, from the Ophthalmology Department at the Istituto Clinico Humanitas, in Milan, Italy.

Corneal collagen cross-linking in children might reduce the need for early penetrating keratoplasty, she said.

Although corneal collagen cross-linking is approved in Europe, it is not yet approved for use in the United States outside clinical trials. This treatment relies on a photochemical reaction, using topical riboflavin and ultraviolet (UV)-A light, to induce cross-linking of the corneal collagen fibers. The goal is to strengthen the cornea and stop progression of the disease.

For this study, Dr. Albé and her colleagues treated 66 eyes with documented progressive keratoconus in patients who ranged in age from 9 to 18 years (mean age, 15 years). To be eligible for the study, the patients' corneal thickness had to be no less than 400 μm at the thinnest point, the standard cutoff considered necessary to ensure that the retina does not absorb UV-A radiation.

After removing the patients' corneal endothelium, the investigators performed corneal cross-linking using the standard procedure. They used the technique described by Dr. Albé and her colleague Paolo Vinciguerra, MD, in the April 2009 issue of Cataract & Refractive Surgery Today Europe: they instilled 0.1% riboflavin in 20% dextran solution each minute for 30 minutes into the corneal stroma to protect the lens and retina from the UV-A, and then applied the solution every 5 minutes for another 30 minutes while the eye was under UV-A irradiation. The researchers measured refractive and tomographic outcomes for 24 months after cross-linking, according to their abstract.

Corneal Steepness Decreases

On average, both uncorrected and best spectacle-corrected visual acuity improved significantly, by at least 2 lines, 2 years after cross-linking, Dr. Albé reported. Spherical equivalent decreased by 0.81 diopters. In addition, keratometry showed that steepness of the cornea decreased by 3 diopters on average.

Although corneal thickness significantly decreased at 1 year, as shown on central pachymetry, there was no statistically significant difference at 2 years, she said. In addition, corneal endothelial cell counts showed no significant difference 2 years after cross-linking, and there was no significant difference between children and adult control subjects who received cross-linking in deep opacities of the corneal stroma after treatment, according to Dr. Albé.

"Corneal collagen cross-linking is indicated in children with progressive keratoconus," Dr. Albé said. She was unavailable for an interview.

"Much Needed" Data

The moderator who discussed the presentation, Terry Kim, MD, professor of ophthalmology at Duke Eye Center, Durham, North Carolina, said that "this study provides much needed data."

Dr. Kim, who did not participate in the study, told Medscape Medical News that "there's nothing published in the pediatric population on the use of collagen cross-linking. [The investigators] had a pretty good number of pediatric patients who underwent cross-linking, they had 24-month follow-up, and they had good results."

He called the data "encouraging," saying that "there's no way to arrest the progression of keratoconus. If you treat this disease at an earlier stage, these patients may have better vision than previous experience has shown."

Researchers, however, do not yet know how long the effects of collagen cross-linking last. In response to Dr. Kim's question during the panel discussion, Dr. Albé replied that if keratoconus progresses, these young patients might need another cross-linking treatment.

Riboflavin Effects

Although riboflavin appears to thin the cornea, Dr. Kim told Medscape Medical News "that thickness seems to come back, at least that's what this study showed."

However, another researcher not involved with the study said in an interview that not all formulations of riboflavin thin the cornea. William Trattler, MD, from the Center for Excellence in Eye Care in Miami, Florida, coauthored a scientific poster also presented at the meeting (Poster 350), in which he and his coworker compared different formulas of 0.1% riboflavin for use with corneal collagen cross-linking.

Dr. Trattler told Medscape Medical News that riboflavin with dextran, which is commercially available in Europe, resulted in an average decrease in corneal thickness of 27.61 μm after removal of the corneal endothelium and 30 minutes of riboflavin instillation (n = 18 eyes, according to the poster). That group's resulting average corneal thickness of 386.28 μm made the patients ineligible for UV-A irradiation. However, the same procedure using specially compounded riboflavin with gum cellulose as the vehicle resulted in an average increase in corneal thickness of 94.54 μm before UV-A irradiation (n = 26 eyes), the authors' data showed.

"When we select the riboflavin drops, we want to select ones that do not thin the cornea and make it unsafe during light treatments," Dr. Trattler said. "If the patient's corneal thickness is close to 400 μm, the best choice would not be the dextran [vehicle] for epithelium-off treatments. It would be gum cellulose."

Dr. Albé and Dr. Kim have disclosed no relevant financial interests. Dr. Trattler reports being a consultant to CXL-USA, which is conducting a multicenter corneal collagen cross-linking study in the United States.

American Academy of Ophthalmology (AAO) and Middle East Africa Council of Ophthalmology (MEACO) 2010 Joint Meeting: PA065. Presented October 18, 2010.


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