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Cornea specialist examines ways to assess keratoconus progression
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In order to decide if and when corneal cross-linking should be performed, cornea specialists need new means and criteria to precisely assess keratoconus progression.
“Measuring progression is nowadays still a challenge. There are several metrics but also many confounding factors, and the technologies we have are still far from perfect,” David Touboul, MD, PhD, of the University of Bordeaux, France, said.
Ten years ago, before cross-linking entered the scene, keratoconus was classified in severity scales according to Amsler-Krumeich, Alió-Shabayek and others. They worked well at the time, when little could be done for the condition apart from monitoring progression and correcting vision with spectacles and contact lenses up to the stage of corneal transplantation.
“Now with CXL we are able to halt progression and need progression rate indexes that are less macroscopically designed,” he said.
Cross-linking has been a big step forward and is now a well-established technique. Still, “we must bear in mind that it is not devoid of complications, and decision-making criteria are needed,” he said.
Refractive, functional parameters
The keratoconus progression rate is not a linear function. Diagnosis is often made in teenagers or young adults, but infancy is the starting point and 88% of pediatric cases will progress. In a study carried out in Bordeaux, a center of reference for keratoconus in Europe, a group of keratoconic children younger than 15 years of age was compared with a group of young adults older than 27 years.
“Slit lamp signs were more frequent in the younger group, disease severity at the time of diagnosis was greater, and progression rate was higher, according to topography data,” Touboul said.
Even in adults, keratoconus tends to progress in about 25% of cases, he said.
Keratoconus progressively changes corneal biomechanics, morphology and function. Classic signs are, in chronological order, biomechanical anisotropy, posterior bulging, anterior bulging and thinning, and eventually refractive changes and visual acuity symptoms, Touboul explained.
He reviewed the current methods to detect and measure these changes, starting with corneal aberrometry. Optical aberrations are measurable and theoretically a good parameter, but currently available wavefront analyzers need standardization.
“Measurements are not consistent between devices. Pupil diameter and accommodation can be confounding factors,” Touboul said.
Visual acuity changes can be easily detected, but variability is an important issue in keratoconus eyes. Fluctuations occur according to light conditions because of corneal varifocality and can also occur with accommodation, eyelid aperture and squeezing of the eye. Furthermore, rigid contact lenses and unilateral disease can mask progression.
“Patients themselves might not become aware of changes in these cases,” Touboul said. “Nevertheless, patients should be carefully heard because their subjective perception and complaints are often more important and reliable than subjective refraction changes.”
Biomechanics
Biomechanical degeneration in keratoconic eyes is often associated with excessive corneal daily stress induced by eye rubbing.
“Eye rubbing is one of the major factors associated with higher progression and is correlated with atopic disease and inflammation molecules in the tear film. It is, however, difficult to quantify,” Touboul said.
In vivo elastography does not yet have the capability of measuring keratoconus progression, he said. The ORA (Reichert) is a valuable tool for evaluating corneal hysteresis in studies and also has glaucoma applications, but it does not have the sensitivity to detect early keratoconus changes in the clinic.
“Early morphological changes induced by keratoconus remain below the threshold of ORA indices changes. The system also failed to demonstrate significant effects produced by the CXL procedure,” Touboul said.
A combination of topography and Corvis ST tonometry (Oculus) has also been attempted, but the algorithm is still not clear.
“All things considered, we cannot say that corneal biomechanics are predictive of the risk to develop posterior ectasia and keratoconus progression,” Touboul said.
Morphological metrics
Morphological metrics are still the gold standard.
Topographic and tomographic analysis is the most commonly used method to rate progression because it correlates well with the progressive worsening of the condition and the decision to halt the disease with surgical methods.
“Morphological metrics are still our best bet for evaluating progression. Over the years we have achieved some consensus on parameters and cutoff values, such as corneal bulging and anterior Kmax of more than 50 D, posterior elevation of more than 50 µm and anterior elevation of more than 40 µm. Corneal thinning parameters are corneal thinnest point of less than 400 µm and corneal asymmetry with irregularity index of more than 6.5 D at 3 mm,” Touboul said.
However, limitations remain: Peripheral changes are not represented, and measurements may be affected by tear film instability, contact lens warpage, epithelial changes and variable deformation according to the eyelid opening during examination, he said.
Using the Galilei G4 system (Ziemer), a prospective observational study including 109 keratoconus patients was carried out at the University of Bordeaux with the aim of finding the earliest parameters that change when keratoconus starts progressing. Patients were monitored monthly for 1 year. Based on the Galilei’s parameters, 13% of the patients were progressive. In that subgroup, posterior keratometry changes were found to manifest earlier than anterior changes, and coma aberration at 6 mm was detected earlier than the usual Kmax at 3 mm.
“Keratoconus is usually looked at through a 3 mm window for progression, but if you enlarge to 6 mm, you can detect earlier signs. To do this, you need elevation rather than specular topography. You need Scheimpflug technology or OCT mapping,” Touboul said.
Stromal pachymetry mapping with high-speed OCT might be a significant step forward in the future, according to Touboul.
“It could enable us to separate stromal changes from epithelial compensation, and we could learn much more about progression because the epithelium masks the changes,” he said.
This technology is still under development. Touboul is currently working to create dedicated software for measuring the stroma. – by Michela Cimberle
- For more information:
- David Touboul, MD, PhD, can be reached at CHU de Bordeaux, site Pellegrin, centre Xavier François Michelet, place Amélie Raba-Léon Bordeaux, 33000 Bordeaux, France; email: david.touboul@chu-bordeaux.fr.
Disclosure: Touboul reports no relevant financial disclosures.