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Improving LASIK outcomes: Addition of CXL for corneal stability


Achieving super-vision after LASIK may rest on the addition of corneal collagen crosslinking around the time of surgery.



Achieving super-vision after LASIK may rest on the addition of corneal collagen crosslinking around the time of surgery.


By Lynda Charters; Reviewed by Ernest W. Kornmehl, MD

Chicago-Ophthalmologists are faced with wound healing and biomechanical changes after wavefront-guided keratorefractive surgery that include mechanical complications related to flap creation in LASIK and optical complications related to decentration, optical zone size, positive asphericity, and uncorrected higher-order aberrations (HOAs).

Despite advances in laser technology-such as iris registration, multifocal ablations, mixed astigmatism, intraoperative pachymetric monitoring, and the introduction of femtosecond laser technology-the complications related to customized LASIK remain. These include flap complications, custom cornea limitations, and ectasia.

The answer to these problems may be the addition of corneal collagen crosslinking (CXL) performed around the time of LASIK, according to Dimitri T. Azar, MD, MBA, dean, University of Medicine, holder of the B.A. Field Chair in Ophthalmologic Research, and professor of ophthalmology, pharmacology, and bioengineering, University of Illinois at Chicago.


Asphericity-based treatments

Dr. Azar and colleagues have focused their research on improving the spherical aberrations, the 10th-order Zernike polynomials. They started initially by approaching the question of whether simply flattening the central cornea during LASIK in patients with myopia creates problems because of the untreated peripheral cornea.

“Are we creating an oblation cornea with a bigger problem?” he asked.

In a cornea that is perfectly spherical (Q = 0), the rays entering through the corneal periphery are bent more and do not meet the para-axial rays, resulting in poorer image quality, he explained. Therefore, slightly flattening the peripheral cornea creates negative asphericity, which results in less bending of the rays after they enter the peripheral cornea.

“A prolate cornea provides better image quality,” Dr. Azar said.


Wavefront- or asphericity-guided treatment

Dr. Azar recounted a study from 2006 in which he and Drs. Sakimoto and Rosenblatt compared the outcomes of custom and non-custom LASIK procedures in published studies. The outcomes that they focused on were the percentages of patients with myopia with 20/20 or better vision, 20/40 or better, within 0.5 or 1 D of the targeted vision, and those who lost two or more lines of Snellen acuity.

When investigators compared the results for patients with 20/40 or better, within 0.5 or 1 Dr of the targeted vision, and those who lost two or more lines of Snellen acuity, there were no differences between custom and non-custom LASIK.

“When we evaluated the patients with better than 20/20 vision, we found differences of about 10% to 12% in favor of customized LASIK procedures regardless of the degree of myopia,” he commented and explained that patients who underwent a customized procedure had a higher probability of achieving 20/20 or better vision.

However, while those results are better in myopic patients compared with non-customized procedure, they still are not achieving super-vision because of limitations in the wavefront analysis.

“Why, despite all of our technologic advances, are we not achieving super-vision?” Dr. Azar posed.

“There are always limitations in customization,” he said. “For example, if the same measurement is performed on the same patient multiple times during the day, the results will differ.”


In addition, there are limitations in the scanning and tracking laser technology that includes patient factors.

More importantly are issues related to postoperative biomechanical changes and wound healing.

“Biomechanics will affect the results especially when procedures go deeper into the cornea,” he said. “Wound healing also affects the results. My thesis is that the two go in opposite directions, especially regarding the diameter of the treatment.”

Dr. Azar explained that there is a relationship between treatment diameter and depth. For example, with a treatment diameter of 6 mm, the depth is about 12 µm per diopter; however, if with a treatment diameter of 8.5 mm, the depth doubles to about 24 µm per diopter.

“Doubling the depth is deleterious for highly myopic patients when performing LASIK,” he said.

Ectasia is a risk in these patients after LASIK even without pre-existing keratoconus, deep flaps, or high myopia even in patients with normal corneas. The potential for development of ectasia ranges from 0.5% to 5% based on surgeon opinion. The basic guideline to follow for LASIK, according to Dr. Azar, is that the cornea is more stable with less tissue ablation.

“Reduce the diameter to reduce ectasia,” he emphasized.

Regarding the effect of wound healing, the epithelial thickness in the treatment zone differs from that in the untreated zone, which applies more to PRK than LASIK. There are biological phenomena going on that change the epithelial thickness, Dr. Azar noted.

He provided the example that with a 5-mm-diameter treatment, 3 microns of tissue hyperplasia will result in loss of the desired treatment effect. Likewise, with an 8-millimeter-diameter treatment, 22 microns of tissue hyperplasia may result.

“In order regain the ability to achieve customization, the treatment should be wider and wider to preserve the effect of customization,” Dr. Azar said. “However, the price of this is weakening of the cornea.

“The effect of the biomechanics and wound healing are pushing surgeons to achieve a certain equilibrium between the two forces,” he said.


What it all comes down to

The resultant question is: Can aspects of conventional surgery, wavefront-guided surgery, and corneal asphericity be combined to provide custom corneal laser treatments?

“The answer to this lies in crosslinking,” Dr. Azar said. “There have been encouraging results of crosslinking in keratoconus. I imagine the day will come when the technology will become part of LASIK.”

Crosslinking has also shown encouraging results in postLASIK ectasia.

Incorporating crosslinking into LASIK will result in the ability to use larger diameter treatments during LASIK to maintain the asphericity of the wavefront-based HOA correction and preserve the good outcomes associated with wavefront-guided treatments without risking development of ectasia, Dr. Azar noted. This process is being referred to currently as high-fidelity LASIK.

Recent advances in laser vision correction-including improved technology, patient selection surface ablation, monovision, and asphericity optimized/wavefront-guided custom LASIK-have allowed for better treatments and outcomes, Dr. Azar summarized.

“Despite the improved outcomes, the limitations include the inability to measure and render all HOAs wavelengths, the inability to predict the surgically induced aberrations, and the inability to perfectly position the treatment on the corneal plane,” he said. “Other important considerations include biomechanical changes and the wound healing effects that take us in the opposite direction from that desired.”

Important needs requiring improvement in what Dr. Azar believes is a “brilliant” future are the need to prevent ectasia, increase corneal rigidity and stability after LASIK, have large optical zones to preserve the intended HOA correction, and have large optical zones to reduce glare and halos.

“These can be accomplished by collagen crosslinking performed at about the time of LASIK,” he said.



Dimitri T. Azar, MD, MBA

E: dazar@uic.edu

This article was adapted from Dr. Azar’s presentation of the Barraquer Lecture at the 2013 meeting of the American Academy of Ophthalmology. Dr. Azar is on the board of directors of Novartis and receives research funding from the National Institutes of Health.


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