To compare the diagnostic efficacy of motion-tracking (MT) Brillouin microscopy with multimodal corneal imaging for keratoconus suspect (KCS) identification.

Prospective, cross-sectional diagnostic evaluation.

There were 56 eyes from 56 patients evaluated, including 28 eyes from 28 bilaterally normal control patients and 28 eyes from 28 keratoconus suspect patients. All patients underwent MT Brillouin microscopy using a custom-built device, Scheimpflug tomography, anterior segment optical coherence tomography (AS-OCT), and Corneal Visualization Scheimpflug Technology (Corvis ST). MT Brillouin microscopy data included mean (MTB-mean) and focal minimum (MTB-min) values within the anterior plateau region. The sensitivity, specificity, and area under the receiver operating characteristic curves (AUROC) were calculated for variables from all modalities.

No significant demographic differences were found between groups except thinnest corneal thickness (556 μm Control vs 526 μm KCS; P < .001). MT Brillouin metrics MTB-min (AUC = 0.999, Sensitivity 100%, Specificity 96%) and MTB-mean (AUC 0.981, Sensitivity 93%, Specificity 100%) outperformed all other multimodal imaging metrics in KCS identification and group differentiation. MTB-min significantly outperformed all multimodal metrics, including the Corvis ST Tomographic and Biomechanical Index (TBI) (AUC 0.906, P = .018), Pentacam Random Forest Index (PRFI) (AUC 0.870, P = .005), Keratoconus Index (KI) (AUC 0.873, P = .005), and Index of Height Decentration (IHD) (AUC 0.859, P = .005). The best epithelial metric, Epi 5 mm ST-IN, performed poorly in group differentiation (AUC = 0.641).

Motion-tracking Brillouin microscopy metrics effectively identified focal corneal weakening in keratoconus suspects and significantly outperformed all multimodal imaging metrics in differentiating keratoconus suspect eyes from normal controls.