Emerging Technology for Detecting Subclinical Keratoconus

In screening laser refractive surgery candidates, distinguishing normal corneas from those with subclinical keratoconus is challenging. Ongoing studies suggest motion-tracking Brillouin microscopy may eventually provide a more reliable method for doing so, says J Bradley Randleman MD.

This optical technology takes advantage of Brillouin light scattering, which detects shifts in optical reflections that correspond with biomechanical differences in tissues. It can measure corneal stiffness in three dimensions without making contact. Motion tracking enables measurement at focal points across the entire cornea, Professor Randleman explained.

In Brillouin microscopy, subclinical keratoconus reveals itself as a softer area in the cornea even though the surrounding tissue is similar to normal corneas. This focal softness may not be enough to show up as differences in corneal steepness or thickness on more conventional topographic or tomographic imaging or air-puff tonometry tests. However, over time, the weaker area will likely deform more under strain than the surrounding stiffer tissue, precipitating ectasia.

Finding 100% specificity and sensitivity

Prof Randleman and colleagues demonstrated the potential for motion-tracking Brillouin microscopy metrics to distinguish subclinical keratoconus in a study comparing 15 eyes with subclinical keratoconus with 15 normal control eyes. All patients underwent Scheimpflug tomography and motion-tracking Brillouin microscopy using a custom-built device. Metrics for each method—as well as specificity and sensitivity for each variable—were then compared for area under the receiver operating characteristic curves.

For the Scheimpflug metrics, significant differences were found between the two groups for thinnest corneal thickness, inferior-superior values, index of vertical asymmetry, and keratoconus index, but for no other metric. The keratoconus index had the highest area under the curve at 0.91, followed by inferior-superior values at 0.89 and index of vertical asymmetry at 0.88.

By contrast, all motion-tracking Brillouin metrics yielded statistically significant differences and fully differentiated between subclinical keratoconus and normal eyes, with areas under the curve of 1.0 and specificity and sensitivity of 100% for each. These included Brillouin mean and minimum values for the anterior plateau and anterior 150 microns.¹

Even individual metrics, such as identifying the softest point on the cornea, reliably distinguished between normal and subclinical keratoconus eyes. “The Brillouin metrics outperformed all the Scheimpflug metrics in this cohort,” Prof Randleman observed.

Moreover, these differences were clearly and consistently visible on two-dimensional Brillouin shift maps. “I would argue it’s fairly easy to tell visually the difference between the normal cornea and the cornea with focal softening, as in the subclinical eyes,” he said.

Prof Randleman and colleagues are conducting further research to develop motion-tracking Brillouin scanning for detecting subclinical keratoconus. Key challenges include increasing the speed of scanning, which takes several minutes with the current device. Nonetheless, the technology shows promise for future clinical use.

Prof Randleman made his comments at Refractive Surgery Day at AAO 2024.

J Bradley Randleman MD is professor of ophthalmology at Case Western Reserve University and co-director of refractive surgery at the Cleveland Clinic, both in Cleveland, Ohio, US, and editor-in-chief of the Journal of Refractive Surgery. randlej@ccf.org

1. Randleman JB, et al. “Subclinical Keratoconus Detection and Characterization Using Motion-Tracking Brillouin Microscopy,” Ophthalmology, 2024; 131(3): 310–321.