Corneal epithelial aberrations: a novel diagnostic tool for keratoconus and forme fruste keratoconus

Abstract Purpose To assess the ability of corneal epithelial aberrations to discriminate forme fruste keratoconus (FFKC) and keratoconus (KC) from normal eyes. Methods This prospective, case-control study enrolled 91 right eyes from 91 normal participants, 87 eyes with FFKC and 148 eyes with KC. Epi...

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Main Authors: Rui Ning, Chak Seng Lei, Xinning Yang, Yue Li, Yizhou Yang, Ingemar Gustafsson, Giacomo Savini, Domenico Schiano-Lomoriello, Xingtao Zhou, Xiaoying Wang, Jinhai Huang
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Language:English
Published: BMC 2025-08-01
Series:Eye and Vision
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Online Access:https://doi.org/10.1186/s40662-025-00449-x
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author Rui Ning
Chak Seng Lei
Xinning Yang
Yue Li
Yizhou Yang
Ingemar Gustafsson
Giacomo Savini
Domenico Schiano-Lomoriello
Xingtao Zhou
Xiaoying Wang
Jinhai Huang
author_facet Rui Ning
Chak Seng Lei
Xinning Yang
Yue Li
Yizhou Yang
Ingemar Gustafsson
Giacomo Savini
Domenico Schiano-Lomoriello
Xingtao Zhou
Xiaoying Wang
Jinhai Huang
author_sort Rui Ning
collection DOAJ
description Abstract Purpose To assess the ability of corneal epithelial aberrations to discriminate forme fruste keratoconus (FFKC) and keratoconus (KC) from normal eyes. Methods This prospective, case-control study enrolled 91 right eyes from 91 normal participants, 87 eyes with FFKC and 148 eyes with KC. Epithelial aberrations for the 6-mm pupil were measured using an anterior segment optical coherence tomography (MS-39, CSO). The epithelial root mean square of higher and lower-order aberrations (total RMS), root mean square of higher-order aberrations (HOAs RMS, from the 3rd to the 7th Zernike polynomials), coma, trefoil, spherical aberration, and secondary astigmatism were recorded. Stepwise logistic regression was utilized to develop the epithelial aberrations index (EAI) for obtaining the optimal discriminant function to diagnose FFKC (EAI-FFKC) and KC (EAI-KC). Area under the receiver operating characteristic curve (AUC) analysis was used to determine the diagnostic accuracy of the indices. Results FFKC and KC eyes had significantly higher epithelial aberrations than normal eyes. Comparing FFKC with the normal group, epithelial HOAs RMS and coma attained AUC values of 0.714 and 0.788, respectively. The EAI-FFKC showed the highest discrimination ability to differentiate FFKC from normal eyes indicated by an AUC value of 0.822 with 77.0% sensitivity and 75.8% specificity. Comparing KC with the normal group, epithelial HOAs RMS attained AUC values of 0.976–0.998 with 95.2%–100% sensitivity and 92.3%–96.7% specificity, epithelial coma attained AUC values of 0.974–0.997 with 92.9%–100% sensitivity and 96.7%–98.9% specificity. The EAI-KC showed the highest discriminative ability to differentiate KC from normal eyes indicated by AUC of 0.996 with 98.6% sensitivity and 98.9% specificity. Conclusion Epithelial wavefront analysis can identify abnormal epithelial changes across all stages of KC, from very early to severe. Epithelial aberrations can be used as a diagnostic tool for KC and FFKC.
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spelling doaj-art-762648b0ec8745ffae56da455565b0bb2025-08-20T04:01:43ZengBMCEye and Vision2326-02542025-08-0112111110.1186/s40662-025-00449-xCorneal epithelial aberrations: a novel diagnostic tool for keratoconus and forme fruste keratoconusRui Ning0Chak Seng Lei1Xinning Yang2Yue Li3Yizhou Yang4Ingemar Gustafsson5Giacomo Savini6Domenico Schiano-Lomoriello7Xingtao Zhou8Xiaoying Wang9Jinhai Huang10Eye Institute and Department of Ophthalmology, NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Eye & ENT Hospital, Fudan University, Chinese Academy of Medical SciencesEye Institute and Department of Ophthalmology, NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Eye & ENT Hospital, Fudan University, Chinese Academy of Medical SciencesSchool of Health Science and Engineering, University of Shanghai for Science and TechnologyEye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical UniversityEye Institute and Department of Ophthalmology, NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Eye & ENT Hospital, Fudan University, Chinese Academy of Medical SciencesDepartment of Clinical Sciences, Ophthalmology, Lund University, Skåne University HospitalG.B. Bietti Foundation I.R.C.C.S.G.B. Bietti Foundation I.R.C.C.S.Eye Institute and Department of Ophthalmology, NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Eye & ENT Hospital, Fudan University, Chinese Academy of Medical SciencesEye Institute and Department of Ophthalmology, NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Eye & ENT Hospital, Fudan University, Chinese Academy of Medical SciencesEye Institute and Department of Ophthalmology, NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Eye & ENT Hospital, Fudan University, Chinese Academy of Medical SciencesAbstract Purpose To assess the ability of corneal epithelial aberrations to discriminate forme fruste keratoconus (FFKC) and keratoconus (KC) from normal eyes. Methods This prospective, case-control study enrolled 91 right eyes from 91 normal participants, 87 eyes with FFKC and 148 eyes with KC. Epithelial aberrations for the 6-mm pupil were measured using an anterior segment optical coherence tomography (MS-39, CSO). The epithelial root mean square of higher and lower-order aberrations (total RMS), root mean square of higher-order aberrations (HOAs RMS, from the 3rd to the 7th Zernike polynomials), coma, trefoil, spherical aberration, and secondary astigmatism were recorded. Stepwise logistic regression was utilized to develop the epithelial aberrations index (EAI) for obtaining the optimal discriminant function to diagnose FFKC (EAI-FFKC) and KC (EAI-KC). Area under the receiver operating characteristic curve (AUC) analysis was used to determine the diagnostic accuracy of the indices. Results FFKC and KC eyes had significantly higher epithelial aberrations than normal eyes. Comparing FFKC with the normal group, epithelial HOAs RMS and coma attained AUC values of 0.714 and 0.788, respectively. The EAI-FFKC showed the highest discrimination ability to differentiate FFKC from normal eyes indicated by an AUC value of 0.822 with 77.0% sensitivity and 75.8% specificity. Comparing KC with the normal group, epithelial HOAs RMS attained AUC values of 0.976–0.998 with 95.2%–100% sensitivity and 92.3%–96.7% specificity, epithelial coma attained AUC values of 0.974–0.997 with 92.9%–100% sensitivity and 96.7%–98.9% specificity. The EAI-KC showed the highest discriminative ability to differentiate KC from normal eyes indicated by AUC of 0.996 with 98.6% sensitivity and 98.9% specificity. Conclusion Epithelial wavefront analysis can identify abnormal epithelial changes across all stages of KC, from very early to severe. Epithelial aberrations can be used as a diagnostic tool for KC and FFKC.https://doi.org/10.1186/s40662-025-00449-xCorneal epithelial aberrationsDiagnosticKeratoconusForme fruste keratoconus
spellingShingle Rui Ning
Chak Seng Lei
Xinning Yang
Yue Li
Yizhou Yang
Ingemar Gustafsson
Giacomo Savini
Domenico Schiano-Lomoriello
Xingtao Zhou
Xiaoying Wang
Jinhai Huang
Corneal epithelial aberrations: a novel diagnostic tool for keratoconus and forme fruste keratoconus
Eye and Vision
Corneal epithelial aberrations
Diagnostic
Keratoconus
Forme fruste keratoconus
title Corneal epithelial aberrations: a novel diagnostic tool for keratoconus and forme fruste keratoconus
title_full Corneal epithelial aberrations: a novel diagnostic tool for keratoconus and forme fruste keratoconus
title_fullStr Corneal epithelial aberrations: a novel diagnostic tool for keratoconus and forme fruste keratoconus
title_full_unstemmed Corneal epithelial aberrations: a novel diagnostic tool for keratoconus and forme fruste keratoconus
title_short Corneal epithelial aberrations: a novel diagnostic tool for keratoconus and forme fruste keratoconus
title_sort corneal epithelial aberrations a novel diagnostic tool for keratoconus and forme fruste keratoconus
topic Corneal epithelial aberrations
Diagnostic
Keratoconus
Forme fruste keratoconus
url https://doi.org/10.1186/s40662-025-00449-x
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