Eight years after he first began stabilizing keratoconic corneas with collagen crosslinking (CXL), corneal surgeon A. John Kanellopoulos, MD, credits the procedure with sparing many patients from undergoing penetrating keratoplasty (PK).
"Today, crosslinking is definitely proving a godsend to people with keratoconus," Dr. Kanellopoulos said in an interview in December 2010. "We see a lot of patients functioning better and their lives improving."
"As a corneal surgeon, I have happily seen my personal volume of cornea transplants for keratoconus drop by 80 percent, even though the number of keratoconic patients we are seeing has increased greatly," he said. "We also are finding that, if crosslinking is offered earlier, these patients do not even need refractive treatment with PRK at all, and their vision stabilizes."
At the LaserVision.gr Institute in Athens, Greece, where Dr. Kanellopoulos is medical director, more than 1,100 people with keratoconus and more than 50 with iatrogenic ectasia have undergone treatment with what is known as "The Athens Protocol": topical riboflavin and ultraviolet A (UVA) irradiation combined with topography-guided photorefractive keratectomy (PRK) to normalize the cornea's shape.
Follow-up is nearing eight years in some of these patients, and the corneas remain stable, said Dr. Kanellopoulos, who is also a clinical professor of ophthalmology at New York University Medical School. He says that it is highly important that surgeons are very conservative with excimer laser ablation when combining crosslinking and PRK.
"You don't want to overtreat the eyes because the corneas already are very thin and you have to anticipate a continuing flattening effect on these corneas from the CXL for several years," Dr. Kanellopoulos said.
Under his protocol, Dr. Kanellopoulos uses an Allegretto Wavelight Eye-Q Excimer Laser (Alcon, Inc.) to plan a customized partial PRK. Doctors at the institute perform an eccentric small optical zone myopic PRK intervention. They use proprietary Wavelight software that combines this myopic PRK with a hyperopic correction that aims to steepen the flattened cornea adjacent to the cone. In this way, the irregular cornea is normalized with minimal tissue removal from the cone. To minimize tissue ablation, Dr. Kanellopoulos removes the epithelium with the excimer laser and decreases the effective optical zone to 5.5 mm, which is 1 mm smaller than in normal eyes.
Using this protocol, he treats only up to 70 percent of the cylinder error and up to 70 percent of the spherical error in order not to remove more than 50 microns of stroma.
"The PRK part should be a very frugal treatment. It is not intended to be a refractive treatment," Dr. Kanellopoulos said. "Its purpose is to reduce irregular astigmatism and normalize the cornea, not to correct refractive error."
The goal, he said, should be improving the patient's best spectacle-corrected visual acuity.
In the early days of crosslinking, Dr. Kanellopoulos introduced a partial topography-guided PRK treatment to follow by as much as 12 months successful stabilization of ectasia with riboflavin/UVA treatment. Combining the procedures, with partial PRK performed first, has been the norm for the last five years.
Other features of the Athens Protocol as currently practiced include:
- use of balanced salt solution (BSS) as the carrier for 0.1% riboflavin sodium phosphate ophthalmic solution (Priavision, Menlo Park, Calif.).
- slight hypotonicity (340 milliosmols) of the solution, which causes the cornea to swell slightly, further protecting the endothelium from the UVA irradiation.
- halving of the UVA treatment time to 15 minutes by doubling the energy output of the UVA diodes to 6 milliwatts per square centimeter.
"We see a significant reduction in the amount of haze by doing them (PRK and crosslinking) together versus doing PRK in a crosslinked cornea," Dr. Kanellopoulos said. "In the patient population in which we did them sequentially separated by six months, we saw more haze than if we had done the procedures together."
Dr. Kanellopoulos suspects that one reason for this difference in haze levels is a reduced numbers of keratocytes after crosslinking.
"It is my impression that when we crosslink cornea, we throw into apoptosis a significant number of keratocytes. For three to six months, the cornea is depleted of these natural healing cells, which if they were present would release the collagen and healing growth factors that lead to haze after PTK (penetrating keratoplasty) and/or PRK," he said.
He explained why: "There is evidence that the more superficial crosslinked area is the strongest. If you were to crosslink the cornea first and then attempt to normalize the cornea with the excimer laser, you would be removing some of the most crosslinked layer that you just created."
If a surgeon decides to perform the procedures six months apart, Dr. Kanellopoulos advises scheduling the crosslinking first. He says that otherwise, PK in an unstabilized cornea might accelerate the keratoconus.
Dr. Kanellopoulos has found that a crosslinked cornea behaves differently than a normal cornea. Consequently, if there is a months-long gap between the surgeries, the surgeon should reduce the refractive target of the ablation beyond the 30 percent reduction that the Athens Protocol recommends for combined procedures, he said.
Financial Disclosures
Dr. Kanellopoulos is a consultant for Alcon, Inc., maker of the Wavelight excimer laser that he uses for topography-guided photorefractive keratectomy.