AUTHOR=Yang Lanting , Xu Hui , Jiang Honghu , Zhu Jingyin , Chen Shihao TITLE=Development and validation of the VAE-NT index: a novel biomechanical parameter for distinguishing subclinical corneal abnormalities JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=Volume 13 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2025.1598546 DOI=10.3389/fbioe.2025.1598546 ISSN=2296-4185 ABSTRACT=PurposeThe aim of this study is to develop an index for distinguishing between very asymmetric ectasia with normal topography (VAE-NT) eyes and normal eyes, with good performance in validity, reliability, and predictive values.MethodsIn the training dataset, this single-center retrospective study involved 102 healthy eyes and 97 VAE-NT eyes. After propensity score matching (PSM), data from 53 healthy eyes and 53 VAE-NT eyes, including demographic and Corvis ST examination results, were collected. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, intraclass correlation coefficient (ICC), and positive and negative likelihood ratios were calculated for the dynamic corneal response (DCR) parameters of Corvis ST. The Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) model was used to objectively and comprehensively evaluate the Corvis ST DCRs, and logistic regression was used to determine the optimal combination of parameters that can accurately separate VAE-NT from normal corneas. In the validation dataset, 44 VAE-NT eyes and 49 normal eyes were involved. The validity, reliability, and predictive value of the index were further assessed using the validation dataset. The VAE-NT index was compared with the tomographic and biomechanical index (TBI) in both the training and validation datasets.ResultsIn the training dataset, the optimal parameter combination forming the VAE-NT index included the following DCRs: SP A1, SP HC, A1 Time, DA Ratio Max (2 mm), DA Ratio Max (1 mm), Integrated Radius, and stress–strain index version 2 (SSI2). The receiver operating characteristic (ROC) curve analysis showed an AUC value of 0.971, with a cut-off value of 0.425, an accuracy of 95.283%, a specificity of 94.340%, and a sensitivity of 96.230%. In the validation dataset, the AUC value of the VAE-NT index was 0.980. The sensitivity and specificity of the VAE-NT index were 93.180% and 95.920%, respectively. The positive and negative likelihood ratios of the VAE-NT index were 22.830 and 0.071, respectively. The ICC of the VAE-NT index was 0.835, and the accuracy was 94.624%. The VAE-NT index outperformed TBI in both the training and validation datasets.ConclusionThe VAE-NT index was developed, exhibiting high sensitivity, specificity, and AUC, along with favorable likelihood ratios and repeatability, suggesting that the VAE-NT index is a robust and reliable tool for distinguishing VAE-NT eyes from normal eyes. Further validation in broader populations and over longer follow-up periods is needed to support clinical translation.