Enhancing Early Keratoconus Detection With Multimodal Machine Learning: Integrating Tomography, Biomechanics, and Clinical Risk Factors

OBJECTIVE

To develop and validate a machine learning (ML) diagnostic system that integrates Scheimpflug tomography, corneal biomechanics, and clinical risk factors (CRF) to enhance the early detection of keratoconus (KC).

DESIGN

Prospective, multicenter, cross-sectional study.

PARTICIPANTS

Patients diagnosed with KC and individuals evaluated in preoperative refractive surgery clinics.

METHODS

Demographic, lifestyle, and clinical ophthalmic data, including Pentacam and Corvis ST measurements, were collected from patients with KC and refractive surgery candidates across 5 centers between 2020 and 2024. The dataset was divided into training, validation, internal test, and external test sets. Least absolute shrinkage and selection operator regression was used to identify predictive variables. Six ML models were trained using 4 feature sets: CRF, device-derived parameters, combined features, and selected features.

MAIN OUTCOME MEASURES

Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC).

RESULTS

The dataset included 1035 eyes from 1035 participants across 5 centers: 590 normal controls, 157 eyes with forme fruste keratoconus (FFKC), 143 with subclinical KC, and 145 with clinical KC. For FFKC detection, the post-feature selection CatBoost model achieved the highest accuracy (AUROC = 0.975), outperforming the combined-feature (AUROC = 0.963), CRF-only (AUROC = 0.856), and device-only models (AUROC = 0.885) in the validation set. This model also outperformed the tomographic and biomechanical index in internal (AUROC = 0.976 vs 0.813; P = .048) and external testing (AUROC = 0.952 vs 0.847; P = .012). For subclinical and clinical KC, external testing yielded near-perfect performance (AUROC = 0.991 and 1.000, respectively).

CONCLUSIONS

A multimodal ML system integrating CRF, tomography, and biomechanics improved early KC detection, particularly for FFKC. This approach may enhance clinical decision-making and screening for refractive surgery candidates.