{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:51:08Z","timestamp":1791615068677,"version":"4.3.4"},"reference-count":37,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: This study quantified the planar distance (D, mm) between the corneal thinnest point (TP) and maximum keratometry (Kmax) and examined its association with tomographic features and keratoconus severity. Methods: Tomographic data from 140 patients (280 eyes) with bilateral manifest keratoconus were obtained with a Scheimpflug camera (Pentacam HR; Oculus, Wetzlar, Germany). D was calculated from the Cartesian coordinates of TP and Kmax. A multiple linear regression model included simulated anterior average keratometry (SimKavg), anterior and posterior radii of curvature (ARC and PRC), and anterior Q-value (Q-ant). Inference used patient-clustered robust standard errors. Internal validation comprised repeated grouped 10-fold cross-validation and patient-level bootstrap resampling. Performance was assessed using R2, root-mean-square error (RMSE), mean absolute error (MAE), and Bland\u2013Altman limits of agreement. Results: The model explained 51.8% of the apparent variance in D (adjusted R2 = 0.511; p &lt; 0.001). Apparent RMSE and MAE were 0.568 and 0.428 mm. Mean grouped cross-validated performance was R2 = 0.472, RMSE = 0.594 mm, and MAE = 0.443 mm. The out-of-fold bias was \u22120.005 mm, with 95% limits of agreement from \u22121.162 to +1.151 mm. ARC, SimKavg, and Q-ant remained significant with patient-clustered inference, whereas PRC did not (p = 0.111). Conclusions: D was associated with keratoconus severity and could be estimated with moderate internal performance from routinely available tomographic variables. Collinearity, fellow-eye dependence, and limits of agreement of approximately \u00b11.1 mm restrict interpretation of individual coefficients and preclude interchangeability with direct measurement. External and longitudinal validation is required before clinical use.<\/jats:p>","DOI":"10.3390\/diagnostics16193194","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:25:44Z","timestamp":1790850344000},"page":"3194","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multivariate Analysis of the Spatial Distance Between the Corneal Thinnest Point and Maximum Keratometry in Keratoconic Corneas: Association with Disease Severity"],"prefix":"10.3390","volume":"16","author":[{"given":"Umberto","family":"Camellin","sequence":"first","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8842-7102","authenticated-orcid":false,"given":"Marco","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Studio Italiano di Oftalmologia, Via Livenza 3, 00198 Rome, Italy"},{"name":"Vision Engineering Italy srl, Via Livenza 3, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Francesco","family":"Franchina","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Ivan","family":"Ninotta","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Gianluigi","family":"Latino","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2834-6142","authenticated-orcid":false,"given":"Antonio","family":"Valastro","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9582-9799","authenticated-orcid":false,"given":"Pasquale","family":"Aragona","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Domenico","family":"Schiano-Lomoriello","sequence":"additional","affiliation":[{"name":"UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy"},{"name":"IRCCS Fondazione G.B. Bietti, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8083-3437","authenticated-orcid":false,"given":"Anna M.","family":"Roszkowska","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy"},{"name":"Faculty of Medicine, Andrzej Frycz Modrzewski Krakow University, 30-705 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101559","DOI":"10.1016\/j.clae.2021.101559","article-title":"Keratoconus: An updated review","volume":"45","author":"Carracedo","year":"2022","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1177\/11206721241235984","article-title":"Estimated prevalence of keratoconus in the largest metropolitan area of Italy","volume":"34","author":"Lombardo","year":"2024","journal-title":"Eur. 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