Adjunctive safety tool proves valuable

Jun 01, 2010

Mapping epithelial thickness in patients with abnormal topography may rule out keratoconus

Eyes categorized as having suspected keratoconus based on corneal topography and subsequently determined to be non-keratoconic by epithelial thickness profile criteria demonstrate good refractive stability after LASIK during up to 2 years of follow-up, said Dan Z. Reinstein, MD, MA(Cantab), FRCSC, FRCOphth.

Professor Reinstein, medical director at the London Vision Clinic, London, presented a 2-year update from a retrospective, case-control study comparing post-LASIK safety and refractive stability.

The study group was composed of 90 eyes with suspected keratoconus confirmed as non-keratoconic by epithelial thickness profile mapping. Their results were compared with those from a control group consisting of eyes matched within 0.50 D for preoperative sphere, cylinder, and spherical equivalent (SE), as well as for age and IOP.

Comparison of the refractive stability of SE and cylinder showed no statistically significant differences between the suspected keratoconus cases and matched controls at any time point during 2 years of post-LASIK follow-up. Analysis of corrected distance visual acuity (CDVA) outcomes also showed no statistically significant differences between groups.

"A diagnostic technique is needed that can definitively establish or rule out a diagnosis of keratoconus in eyes with abnormal topography when assessing patient suitability for LASIK, and I believe that epithelial thickness profiles can help provide the answer," Professor Reinstein said.

Epithelial thickness profiles

In previous research, Professor Reinstein and colleagues demonstrated that the epithelium of the average normal human cornea was not uniform in thickness, but rather, the epithelium was on average thinner superiorly and thicker inferiorly.2

This contrasted with keratoconic eyes, in which the epithelial thickness map exhibited a donut pattern characterized by thinning at the apex of the cone surrounded by an annulus of thicker epithelium.3

Professor Reinstein and colleagues hypothesize that front and back corneal surfaces are generally yoked, meaning that any back surface ectatic change will be accompanied by a front stromal surface ectatic change.

In early keratoconus, epithelial changes could potentially fully compensate for the stromal surface irregularity and render a completely normal front surface topography, whereas the ectasia would still be apparent on the posterior surface elevation best fit sphere, he explained.

"Because the Artemis can measure changes of as little as 1 µm within the epithelial layer, the very earliest changes in the epithelial thickness profile in response to a front surface stromal cone can be detected," he said.

"Therefore, a localized zone of epithelial thinning overlying a posterior corneal surface eccentric apex would indicate an associated anterior stromal cone.

"Effectively, the epithelial thickness profile adds extra information to what is provided by front and back surface topography, making the diagnosis or exclusion of keratoconus more specific," he added.

Stability of LASIK

For this study of LASIK stability, researchers included eyes identified from a series of 1532 consecutive myopic eyes that had been evaluated with the London Vision Clinic's standard topographic screening protocol for LASIK eligibility. This screening protocol uses two topography systems (Atlas Corneal Topography System, Carl Zeiss Meditec; Orbscan II Topography System by Orbtek, Bausch + Lomb). A total of 136 eyes (9.2%) were classified as having suspected keratoconus and scanned with the Artemis for epithelial thickness mapping. Twenty-two (16%) of the 136 eyes were diagnosed as having keratoconus and excluded from LASIK.

"Keratoconus was confirmed on epithelial thickness mapping if there was relative epithelial thinning correspondent to an eccentric posterior elevation best-fit sphere apex," Professor Reinstein said. Of the remaining 114 eyes, 90 underwent LASIK and 24 had PRK.

"For the purpose of our retrospective case-control analysis of post-refractive surgery stability, we chose to look at the eyes that had undergone LASIK, as this procedure would be expected to destabilize the cornea more than PRK and so if ectasia were to occur, it would develop sooner," Professor Reinstein said.

Preoperatively, mean SE was –3.78 D, mean cylinder was 1.02 D, and mean IOP was 14 mmHg for the suspected keratoconus group, and were nearly identical in the control group. Data was available in 94% of eyes at 1 year and 85% of eyes at 2 years for the suspected keratoconus group, while data was available in 100% of eyes in the control group at both 1 and 2 years.

At 2 years, both the suspected keratoconus and control groups showed similar, small myopic shifts, compared with the 3-month visit (–0.17 and –0.10 D, respectively).

However, there was no statistically significant difference between groups in the magnitude of the change. Graphs of spherical equivalent stability at 1, 3, 6, 12 and 24 months for the two groups were essentially overlapping, and there were no statistically significant differences between groups in mean spherical equivalent at any time point.

Vector analysis was used to evaluate cylinder stability. The results showed no statistically significant differences between the suspected keratoconus and control groups in mean magnitude or axis at any of the postoperative visits or in the changes between 3 and 24 months.

Analysis of changes from preoperative CDVA also showed no significant differences between groups. At 2 years, rates of 1-line loss were the same between groups (5% in suspected keratoconus and 2% in the controls). No eyes lost more than 1 line of CDVA, and similar proportions of patients with suspected keratoconus and controls gained 1 or more lines (39% and 43%, respectively).

"Suspected keratoconus diagnosed as non-keratoconic by using epithelial thickness mapping demonstrated equal stability and refractive outcomes as control eyes at 24 months," he said. "Epithelial thickness mapping may enable us to perform LASIK confidently in eyes that otherwise would not have been considered for LASIK.

"We recognize that ectasia may take up to several years before it is identified, and we will continue to monitor this population carefully to document long-term stability," Professor Reinstein concluded. "I am quite convinced that epithelial thickness mapping will be the next most powerful diagnostic tool to the corneal and refractive surgeon since topography of the back surface was introduced."


1. D.Z. Reinstein, T.J. Archer and M. Gobbe, J. Refract. Surg., 2009;25:569–577.

2. D.Z. Reinstein et al., J. Refract. Surg., 2008;24:571–581.

3. D.Z. Reinstein et al., Epithelial, stromal and corneal thickness in the keratoconic cornea: three-dimensional display with Artemis very high-frequency digital ultrasound. J. Refract. Surg., 2009 [Online].