Correlative Characteristics of Multidimensional Clinical Parameters and Predictive Value of Epithelial Thickness Variation in Chinese Patients with Keratoconus

Correlative Characteristics of Multidimensional Clinical Parameters and Predictive Value of Epithelial Thickness Variation in Chinese Patients with Keratoconus | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Correlative Characteristics of Multidimensional Clinical Parameters and Predictive Value of Epithelial Thickness Variation in Chinese Patients with Keratoconus LIU LIU, Lin Jiang, yanlan Ding, Jing Tang, xingtao Zhou, chunyi Gui, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8952134/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Keratoconus (KC) is a bilateral, progressive, and non-inflammatory corneal ectatic disorder. This study aimed to characterize disease-specific features of KC in a Chinese population and analyze correlations among multidimensional clinical parameters using a large-scale clinical dataset, to support precision clinical screening and personalized treatment strategies. Methods Clinical records of 1,219 patients with KC treated between January 2019 and December 2023 were retrospectively analyzed. Collected variables included demographic characteristics, axial length (AL), intraocular pressure, and corneal parameters, including morphology and epithelial thickness. Statistical analyses were performed using SPSS version 26.0. Pearson’s correlation analysis was used to assess linear relationships between continuous variables, while one-way analysis of variance followed by Tukey’s honest significant difference post-hoc test were used to compare differences among the KC severity groups. Results The mean patient age was 22.32 ± 6.65 years, with adolescents and young adults accounting for more than 80% of the cohort. Unilateral surgery was performed in 90.0% of the cases, with a median interval of 17 days between bilateral procedures. The thinnest corneal point was predominantly located inferotemporally (right eye mean vector: 0.34 ± 0.22; left eye mean vector: 0.73 ± 0.26). The AL was significantly shorter in the maximum keratometry (Kmax) ≥ 58 D group than in the Kmax < 48 D group (P 490 µm group than in the groups with TCT < 490 µm (P < 0.01). Non-contact tonometry exhibited a strong negative correlation with Kmax (r = -0.7) and a strong positive correlation with the TCT (r = 0.61). Among epithelial parameters, the difference between the minimum and maximum corneal epithelial thickness demonstrated the strongest correlation with Kmax (r = -0.83). Conclusions KC in the Chinese population is characterized by a marked clustering in adolescence and a tendency toward initial unilateral presentation. Shorter AL may be associated with an increased risk of severe disease. Corneal epithelial thickness variation, particularly the minimum–maximum difference, serves as a highly sensitive indicator of KC severity, offering valuable insights for the development of precision screening and early intervention strategies. keratoconus axial length corneal epithelial thickness variation predictive indicator Figures Figure 1 Figure 2 Figure 3 Figure 4 BACKGROUND Keratoconus (KC) is a bilateral, non-inflammatory, and progressive corneal ectatic disorder characterized by corneal thinning and cone-like protrusions, with a reported prevalence of approximately 1 in 2,000 in the general population [ 1 ]. Its pathogenesis involves a complex interplay of genetic, environmental, and corneal biomechanical factors. However, disease-specific clinical characteristics, patterns of interrelationships among clinical parameters, and sensitive predictive indicators for the Chinese population with KC remain insufficiently characterized [ 2 ]. Existing research has predominantly focused on isolated associations between individual parameters and disease status, lacking a systematic and integrated analysis of multidimensional parameters, such as axial length (AL), intraocular pressure (IOP), and corneal epithelial thickness variations [ 3 ]. Building on our extensive experience in KC research, including pioneering work on epithelium-off-accelerated corneal cross-linking in China, our study moves beyond traditional single-parameter analyses. This study aimed to characterize disease-specific patterns in a Chinese population by integrating demographic features, corneal morphology, AL, and IOP from a large clinical cohort, particularly focusing on the clinical value of corneal epithelial thickness variation. The primary objective was to identify highly sensitive indicators of disease severity, thereby providing a theoretical and clinical basis for early screening, personalized treatment, and prognostic assessment. METHODS Study Population This retrospective study included 1,219 patients diagnosed with KC at our hospital between January 2019 and December 2023. Patients aged 5–60 years who met the established diagnostic criteria for KC were included. The exclusion criteria were the presence of other organic ocular or systemic diseases, autoimmune disorders, or psychiatric conditions. This study adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of the Eye & ENT Hospital of Fudan University.Informed consent to participate was obtained from the parents or legal guardians of any participant under the age of 18. Clinical Examinations All patients underwent comprehensive ophthalmic examinations, including slit-lamp microscopy, refraction, IOP measurement using noncontact tonometry (NCT, mmHg), and AL measurement (mm). A Pentacam system (Oculus Optikgeräte GmbH, Wetzlar, Germany) was used to measure the maximum anterior keratometry (Kmax, D), central corneal thickness (CCT, µm), thinnest corneal thickness (TCT, µm), and apical corneal thickness (ACT, µm). The location of the thinnest point was recorded as its displacement from the corneal apex (mm). Corneal epithelial thickness was measured within a 5-mm central zone using optical coherence tomography. The minimum and maximum epithelial thickness values within this zone were extracted to calculate the minimum-maximum (min-max) epithelial thickness difference (µm). Statistical Analysis Data were analyzed using the SPSS software (version 26.0; IBM Corp., Armonk, NY, USA). Descriptive statistics were used to describe the basic characteristics of the data. Pearson’s correlation analysis was performed to assess linear relationships between continuous variables. One-way analysis of variance was used to compare differences among groups, followed by Tukey’s honest significant difference post-hoc test for multiple comparisons. Statistical significance was set at P < 0.05. RESULTS Demographic and Surgical Characteristics The mean age of the patients was 22.32 ± 6.65 years (median: 22 years), with 68.3% of patients aged 17–26 years (interquartile range). The overall age range was 8–56 years, with a peak incidence in adolescence and young adulthood. Unilateral surgery was performed in 1,098 patients (90.0%), while bilateral surgery was performed in 121 patients (9.9%). For bilateral procedures, the mean interval between surgeries was 55.74 ± 105.87 days, with a median of 17 days (range: 0–624 days). Corneal Morphological Features The thinnest corneal point was predominantly displaced inferotemporally in both eyes.(Figure 1 )The mean difference between the CCT and TCT was 18.68 ± 18.79 µm (median: 13 µm), and the mean difference between the ACT and TCT was 7.94 ± 11.45 µm (median: 6 µm). Correlation Analysis of Multidimensional Parameters AL and Disease Severity The direct correlations between the AL and corneal thickness parameters (CCT and TCT) were weak (r = 0.06–0.08). However, the AL varied significantly across disease severity groups (P 490 µm group (25.41 ± 1.12 mm) than in the TCT 400–490 µm (25.14 ± 1.20 mm, P 58 D group (25.08 ± 1.13 mm) than in the Kmax < 48 D (25.51 ± 1.15 mm, P < 0.01) and Kmax 48–53 D groups (25.29 ± 1.16 mm, P = 0.04). Table 1 Axial length (AL) in different thinnest corneal thickness (TCT) and maximum keratometry (Kmax) groups. Group AL(mm) Mean ± SD TCT(µm) 490 25.41 ± 1.12 Kmax(D) > 58 25.08 ± 1.13 53–58 25.04 ± 1.14 48–53 25.29 ± 1.16 < 48 25.51 ± 1.15 IOP and Corneal Parameters NCT measurements demonstrated a strong negative correlation with Kmax (r = -0.7, P < 0.001) and a strong positive correlation with the TCT (r = 0.61, P < 0.001), indicating that lower NCT values were associated with higher Kmax and thinner corneas.(Figure 3 ) Corneal Epithelial Thickness Variation The minimum epithelial thickness within the central 5-mm zone (Epi-Min) demonstrated a strong positive correlation with the CCT (r = 0.9) and TCT (r = 0.95). Notably, the min-max epithelial thickness difference demonstrated the strongest correlation with Kmax (r = -0.83), which was significantly higher than that of other parameters .(Figure 4 ) DISCUSSION Disease-Specific Characteristics of KC in Chinese Youth and Clinical Implications This study is the first to identify two prominent clinical features of KC in the Chinese population: clustering in adolescence and a tendency toward unilateral initial presentation. The mean patient age was 22.32 years, with more than two-thirds of the patients aged 17–26 years. Furthermore, 90.0% of the patients underwent unilateral surgery, which contrasts with the more frequently reported bilateral synchronous involvement in Western populations [ 4 , 5 ]. This finding suggests that KC presentation in Chinese adolescents may be associated with population-specific genetic susceptibility in East Asian populations, as well as ocular developmental factors during adolescence, and behavioral influences, including eye rubbing [ 6 – 8 ]. The relatively low proportion of bilateral surgery (10%) suggests that simultaneous progression in both eyes may be less common, underscoring the importance of close longitudinal monitoring of the fellow eye to detect disease progression while avoiding unnecessary interventions in the fellow eye. Correlation Between AL and KC Severity KC is primarily driven by structural abnormalities in corneal stromal collagen, while axial elongation has been linked to reduced scleral collagen fiber strength [ 9 ]. With advancements in anterior segment imaging and biometry, increasing attention has been directed toward the relationship between the entire ocular structure, including the AL, and KC pathogenesis [ 10 , 11 ]. Although previous studies focused on direct correlations between the AL and corneal thickness, our study found that this link is weak (r = 0.06–0.08). Notably, the AL differed significantly across disease severity strata, with shorter AL observed in patients with more severe KC (higher Kmax and thinner TCT). This finding is consistent with that of a large population-based study published in 2023, which reported shorter AL as a significant risk factor for KC prevalence [ 12 ]. Our study is the first to report a correlation between the severity of KC and AL. These results suggests that the AL may influence KC severity indirectly through alterations in the biomechanical environment of the eye rather than through direct effects on corneal thickness, thereby providing a new target for clinical intervention strategies. Patients with similar KC severity but shorter AL may signify a higher risk of progression, warranting closer monitoring. Predictive Value of Corneal Epithelial Thickness Variation This study is the first to report a very strong negative correlation between the min-max epithelial thickness difference and Kmax (r = -0.83), which is significantly stronger than that observed for traditional parameters (e.g., TCT vs. Kmax, r ≈ -0.7). This finding indicates that epithelial thickness heterogeneity (degree of variation) may be a more sensitive marker of ectatic severity than absolute thickness values alone. The outermost protective layer of the corneal epithelium plays a crucial role in maintaining corneal biomechanical stability [ 13 ]. During KC progression, the epithelium thins over the apex of the cone owing to mechanical stretching, accompanied by compensatory thickening in the periphery, resulting in an increased min–max difference. This change in the thickness variation often precedes significant alterations in the corneal stroma, serving as a "sensitive signal" for early disease progression [ 14 ]. Compared with traditional parameters, such as Kmax and TCT, the min–max difference is a noninvasive and more sensitive metric, making it a promising metric for early screening, disease monitoring, and postoperative follow-up, particularly in adolescent patients. Bidirectional Regulatory Relationship Between IOP and Corneal Parameters Our study confirmed a strong negative correlation between NCT and Kmax and a strong positive correlation between NCT and TCT, highlighting the complex interaction between IOP measurement corneal biomechanics in KC. Corneal thinning and biomechanical weakening in KC result in systematic underestimation of the IOP. The American Academy of Ophthalmology 2024 Clinical Practice Guidelines for Corneal Ectasia state that IOP measurements using applanation tonometers (e.g., Goldmann) are artificially low in ectatic diseases owing to tissue thinning and biomechanical weakening. The guidelines recommend using alternative devices that are less dependent on corneal regularity, such as pneumatic, thickness-compensating, dynamic contour, or rebound tonometers and emphasize the loss of corneal resistance when interpreting IOP readings. A 2023 study also found that NCT measurements increased significantly after corneal crosslinking, an effect that was attributed to increased corneal stiffness [ 15 ]. Taken together, these findings emphasize that accurate IOP assessment in patients with KC requires consideration of corneal biomechanical properties, and advanced approaches such as biomechanically corrected IOP measurements using Corvis ST may offer superior clinical utility. CONCLUSIONS KC in the Chinese population presents is characterized by adolescent clustering and a tendency towards initial unilateral presentation. A shorter axial length may be associated with an increased risk of disease progression. The min-max corneal epithelial thickness difference represents a highly sensitive indicator of disease severity. Future studies should further explore the influence of genetic and environmental factors on disease progression to inform optimized prevention and control strategies. Large-scale, multicenter studies incorporating genetic analyses and environmental exposure assessments are warranted to achieve a comprehensive understanding of the pathogenesis and progression of KC. Such efforts may provide a robust scientific foundation for precise diagnosis and personalized treatment, thereby supporting improved ocular health outcomes in the Chinese population. Abbreviations ACT apical corneal thickness AL axial length IOP intraocular pressure KC keratoconus Kmax maximum keratometry NCT non-contact tonometry TCT thinnest corneal thickness Declarations Ethics Approval and Consent to Participate This retrospective study was approved by the ethics committee of the Eye and ENT Hospital affiliated with the Fudan Institutional Review Board (ethical code 2021118-1 ). This study was conducted according to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants after a detailed explanation of the study design. Consent for Publication Not applicable Competing Interests The authors declare that they have no competing interests. Disclosure The funders had no role in the study design, data collection and analysis, decision to publish, or manuscript preparation. Funding This work was supported by the National Key Research and Development Program of China (Grant No. 2023YFA0915000), Key Project of the Regional Innovation and Development Joint Fund of the National Natural Science Foundation of China (Grant No. U24A20708), Zhi Xing Shi Jie - Ophthalmic Clinical Research Support Project (Grant No.BFC-KECS-LC-20251022-03), and Shanghai Engineering Research Center of Laser and Autostereoscopic 3D for Vision Care (20DZ2255000). Author Contribution Study concept and design (LL, LJ, CYG, XYZ,); data collection (LL, LJ, YLD, JT); data analysis and interpretation (LL, XYZ); drafting of the manuscript (LL, LJ); critical revision of the manuscript (XYZ, CYG,); supervision (XTZ, CYG, XYZ). All authors read and approved the final manuscript. Data Availability The data used in this study are available from the corresponding author upon request. References Sriranganathan A, Chan CC, Dhillon J, Felfeli T. Global Incidence and Prevalence of Keratoconus: A Systematic Review and Meta-Analysis. Cornea. 2025 Aug 20. 10.1097/ICO.0000000000003973 . Epub ahead of print. PMID: 40833011. de Azevedo Magalhães O, Gonçalves MC, Gatinel D. The role of environment in the pathogenesis of keratoconus. Curr Opin Ophthalmol. 2021;32(4):379–384. 10.1097/ICU.0000000000000764 . PMID: 33966012. Padmanabhan P, Lopes BT, Eliasy A, Abass A, Vinciguerra R, Vinciguerra P, Ambrósio R Jr, Elsheikh A. Evaluation of corneal biomechanical behavior in vivo for healthy and keratoconic eyes using the stress-strain index. J Cataract Refract Surg. 2022;48(10):1162–1167. 10.1097/j.jcrs.0000000000000945 . PMID: 35333824. Yang K, Xu L, Fan Q, Gu Y, Zhang B, Meng F, Zhao D, Pang C, Ren S. A hospital-based study on clinical data, demographic data and visual function of keratoconus patients in Central China. Sci Rep. 2021;11(1):7559. 10.1038/s41598-021-87291-y . PMID: 33824422; PMCID: PMC8024332. Mou Y, Qin Q, Huang X, Jin X. Risk factors and severity of keratoconus on the East Coast of China. Int Ophthalmol. 2022;42(7):2133–40. 10.1007/s10792-022-02212-w . Epub 2022 Jan 17. PMID: 35038123. Hosoda Y, Miyake M, Meguro A, et al. Keratoconus-susceptibility gene identification by corneal thickness genome-wide association study and artificial intelligence IBM Watson. Commun Biol. 2020;3(1):410. 10.1038/s42003-020-01137-3 . PMID: 32737415; PMCID: PMC7395727. McMonnies CW, Boneham GC. Keratoconus, allergy, itch, eye-rubbing and hand-dominance. Clin Exp Optom. 2003;86(6):376 – 84. 10.1111/j.1444-0938.2003.tb03082.x . PMID: 14632614. Santodomingo-Rubido J, Carracedo G, Suzaki A, Villa-Collar C, Vincent SJ, Wolffsohn JS. Keratoconus: An updated review. Cont Lens Anterior Eye. 2022;45(3):101559. 10.1016/j.clae.2021.101559 . Sedaghat MR, Momeni-Moghaddam H, Azimi A et al. Corneal Biomechanical Properties in Varying Severities of Myopia. Front Bioeng Biotechnol. 2021;8:595330. 10.3389/fbioe.2020.595330 . PMID: 33553113; PMCID: PMC7859342. Averich VV, Avetisov SE, Voronin GV. [Results of optical coherence tomography of the retina and optic nerve in keratoconus]. Vestn Oftalmol. 2021;137(5.Vyp.2):275–280. Russian. 10.17116/oftalma2021137052275 . PMID: 34669338. Bataille L, Molina-Martín A, Piñero DP. Relationship between Axial Length and Corneo-Scleral Topography: A Preliminary Study. Diagnostics (Basel). 2021;11(3):542. 10.3390/diagnostics11030542 . Published 2021 Mar 18. Bikbov MM, Kazakbaeva GM, Gilmanshin TR et al. Prevalence and Associations of Keratoconus Among Children, Adults, and Elderly in the Population-Based Ural Eye Studies.AsiaPacJOphthalmol(Phila).2023;12(6):591–60310.1097/APO.0000000000000639 Wang Q, Deng Y, Li S, et al. Corneal biomechanical changes in allergic conjunctivitis. Eye Vis (Lond). 2021;8(1):17. 10.1186/s40662-021-00241-7 . Published 2021 May 3. Sukhee N, Namba H, Ikeda M et al. Corneal epithelium is altered in keratoconus and forme fruste keratoconus. Sci Rep. 2025;15(1):22203. Published 2025 Jul 1. 10.1038/s41598-025-07663-6 Nabil KM, Elmassry AAK, Ntakarusho S, Said AA. Intraocular pressure after combined photorefractive keratectomy and corneal collagen cross-linking for keratoconus. Int Ophthalmol. 2023;43(12):4837–49. 10.1007/s10792-023-02886-w . Epub 2023 Oct 20. PMID: 37861937; PMCID: PMC10724307. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8952134","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":612310008,"identity":"9f8c3393-a016-451c-8ef4-bef48ebdbfc3","order_by":0,"name":"LIU LIU","email":"","orcid":"","institution":"University of Shanghai for Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"LIU","middleName":"","lastName":"LIU","suffix":""},{"id":612310013,"identity":"1bd1e2a5-0570-46eb-b5bb-f3cbd0fc161f","order_by":1,"name":"Lin Jiang","email":"","orcid":"","institution":"Department of Nursing, Eye \u0026 ENT Hospital, Fudan 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2","display":"","copyAsset":false,"role":"figure","size":394828,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation analysis of the axial length (AL) with different groups of thinnest corneal thickness (TCT) and maximum keratometry (Kmax)\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8952134/v1/b35e70d945c83e68368d5243.png"},{"id":105571154,"identity":"f841a96b-2a00-4cdb-986b-c30894a67116","added_by":"auto","created_at":"2026-03-27 13:21:51","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":310795,"visible":true,"origin":"","legend":"\u003cp\u003eNon-contact tonometry (NCT) in the different thinnest corneal thickness (TCT) and maximum keratometry (Kmax) groups\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8952134/v1/0ecdaf7f2b37b0b8a48c3f30.png"},{"id":105571389,"identity":"9093c123-86cb-444e-9469-3cb75354f57d","added_by":"auto","created_at":"2026-03-27 13:22:54","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1072559,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation analysis of the minimum epithelial thickness (central 5 mm) and min–max epithelial thickness differences with the maximum keratometry (Kmax), central corneal thickness (CCT), and thinnest corneal thickness (TCT)\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8952134/v1/da740a1db37f81f2645f3db1.png"},{"id":108805619,"identity":"adbaac0f-baf4-4e91-b7bd-289cc6c19ff8","added_by":"auto","created_at":"2026-05-08 15:26:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2121376,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8952134/v1/5b502bea-53d9-4104-9e5e-6b7d004398c0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Correlative Characteristics of Multidimensional Clinical Parameters and Predictive Value of Epithelial Thickness Variation in Chinese Patients with Keratoconus","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eKeratoconus (KC) is a bilateral, non-inflammatory, and progressive corneal ectatic disorder characterized by corneal thinning and cone-like protrusions, with a reported prevalence of approximately 1 in 2,000 in the general population [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Its pathogenesis involves a complex interplay of genetic, environmental, and corneal biomechanical factors. However, disease-specific clinical characteristics, patterns of interrelationships among clinical parameters, and sensitive predictive indicators for the Chinese population with KC remain insufficiently characterized [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Existing research has predominantly focused on isolated associations between individual parameters and disease status, lacking a systematic and integrated analysis of multidimensional parameters, such as axial length (AL), intraocular pressure (IOP), and corneal epithelial thickness variations [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBuilding on our extensive experience in KC research, including pioneering work on epithelium-off-accelerated corneal cross-linking in China, our study moves beyond traditional single-parameter analyses. This study aimed to characterize disease-specific patterns in a Chinese population by integrating demographic features, corneal morphology, AL, and IOP from a large clinical cohort, particularly focusing on the clinical value of corneal epithelial thickness variation. The primary objective was to identify highly sensitive indicators of disease severity, thereby providing a theoretical and clinical basis for early screening, personalized treatment, and prognostic assessment.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eThis retrospective study included 1,219 patients diagnosed with KC at our hospital between January 2019 and December 2023. Patients aged 5\u0026ndash;60 years who met the established diagnostic criteria for KC were included. The exclusion criteria were the presence of other organic ocular or systemic diseases, autoimmune disorders, or psychiatric conditions. This study adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of the Eye \u0026amp; ENT Hospital of Fudan University.Informed consent to participate was obtained from the parents or legal guardians of any participant under the age of 18.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eClinical Examinations\u003c/h3\u003e\n\u003cp\u003eAll patients underwent comprehensive ophthalmic examinations, including slit-lamp microscopy, refraction, IOP measurement using noncontact tonometry (NCT, mmHg), and AL measurement (mm). A Pentacam system (Oculus Optikger\u0026auml;te GmbH, Wetzlar, Germany) was used to measure the maximum anterior keratometry (Kmax, D), central corneal thickness (CCT, \u0026micro;m), thinnest corneal thickness (TCT, \u0026micro;m), and apical corneal thickness (ACT, \u0026micro;m). The location of the thinnest point was recorded as its displacement from the corneal apex (mm). Corneal epithelial thickness was measured within a 5-mm central zone using optical coherence tomography. The minimum and maximum epithelial thickness values within this zone were extracted to calculate the minimum-maximum (min-max) epithelial thickness difference (\u0026micro;m).\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were analyzed using the SPSS software (version 26.0; IBM Corp., Armonk, NY, USA). Descriptive statistics were used to describe the basic characteristics of the data. Pearson\u0026rsquo;s correlation analysis was performed to assess linear relationships between continuous variables. One-way analysis of variance was used to compare differences among groups, followed by Tukey\u0026rsquo;s honest significant difference post-hoc test for multiple comparisons. Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and Surgical Characteristics\u003c/h2\u003e \u003cp\u003eThe mean age of the patients was 22.32\u0026thinsp;\u0026plusmn;\u0026thinsp;6.65 years (median: 22 years), with 68.3% of patients aged 17\u0026ndash;26 years (interquartile range). The overall age range was 8\u0026ndash;56 years, with a peak incidence in adolescence and young adulthood. Unilateral surgery was performed in 1,098 patients (90.0%), while bilateral surgery was performed in 121 patients (9.9%). For bilateral procedures, the mean interval between surgeries was 55.74\u0026thinsp;\u0026plusmn;\u0026thinsp;105.87 days, with a median of 17 days (range: 0\u0026ndash;624 days).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCorneal Morphological Features\u003c/h2\u003e \u003cp\u003eThe thinnest corneal point was predominantly displaced inferotemporally in both eyes.(Figure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)The mean difference between the CCT and TCT was 18.68\u0026thinsp;\u0026plusmn;\u0026thinsp;18.79 \u0026micro;m (median: 13 \u0026micro;m), and the mean difference between the ACT and TCT was 7.94\u0026thinsp;\u0026plusmn;\u0026thinsp;11.45 \u0026micro;m (median: 6 \u0026micro;m).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCorrelation Analysis of Multidimensional Parameters\u003c/h3\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eAL and Disease Severity\u003c/h2\u003e \u003cp\u003eThe direct correlations between the AL and corneal thickness parameters (CCT and TCT) were weak (r\u0026thinsp;=\u0026thinsp;0.06\u0026ndash;0.08). However, the AL varied significantly across disease severity groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). As shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the AL was significantly longer in the TCT\u0026thinsp;\u0026gt;\u0026thinsp;490 \u0026micro;m group (25.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12 mm) than in the TCT 400\u0026ndash;490 \u0026micro;m (25.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1.20 mm, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and TCT 300\u0026ndash;400 \u0026micro;m groups (25.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93 mm, *P* = 0.01). Furthermore, the AL was significantly shorter in the Kmax\u0026thinsp;\u0026gt;\u0026thinsp;58 D group (25.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13 mm) than in the Kmax\u0026thinsp;\u0026lt;\u0026thinsp;48 D (25.51\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15 mm, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and Kmax 48\u0026ndash;53 D groups (25.29\u0026thinsp;\u0026plusmn;\u0026thinsp;1.16 mm, P\u0026thinsp;=\u0026thinsp;0.04).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAxial length (AL) in different thinnest corneal thickness (TCT) and maximum keratometry (Kmax) groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAL(mm) Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTCT(\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.11\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e300\u0026ndash;400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e400\u0026ndash;490\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1.20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;490\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eKmax(D)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e53\u0026ndash;58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48\u0026ndash;53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.29\u0026thinsp;\u0026plusmn;\u0026thinsp;1.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.51\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eIOP and Corneal Parameters\u003c/h2\u003e \u003cp\u003eNCT measurements demonstrated a strong negative correlation with Kmax (r = -0.7, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and a strong positive correlation with the TCT (r\u0026thinsp;=\u0026thinsp;0.61, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indicating that lower NCT values were associated with higher Kmax and thinner corneas.(Figure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eCorneal Epithelial Thickness Variation\u003c/h2\u003e \u003cp\u003eThe minimum epithelial thickness within the central 5-mm zone (Epi-Min) demonstrated a strong positive correlation with the CCT (r\u0026thinsp;=\u0026thinsp;0.9) and TCT (r\u0026thinsp;=\u0026thinsp;0.95). Notably, the min-max epithelial thickness difference demonstrated the strongest correlation with Kmax (r = -0.83), which was significantly higher than that of other parameters .(Figure \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eDisease-Specific Characteristics of KC in Chinese Youth and Clinical Implications\u003c/h2\u003e \u003cp\u003eThis study is the first to identify two prominent clinical features of KC in the Chinese population: clustering in adolescence and a tendency toward unilateral initial presentation. The mean patient age was 22.32 years, with more than two-thirds of the patients aged 17\u0026ndash;26 years. Furthermore, 90.0% of the patients underwent unilateral surgery, which contrasts with the more frequently reported bilateral synchronous involvement in Western populations [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This finding suggests that KC presentation in Chinese adolescents may be associated with population-specific genetic susceptibility in East Asian populations, as well as ocular developmental factors during adolescence, and behavioral influences, including eye rubbing [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The relatively low proportion of bilateral surgery (10%) suggests that simultaneous progression in both eyes may be less common, underscoring the importance of close longitudinal monitoring of the fellow eye to detect disease progression while avoiding unnecessary interventions in the fellow eye.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eCorrelation Between AL and KC Severity\u003c/h2\u003e \u003cp\u003eKC is primarily driven by structural abnormalities in corneal stromal collagen, while axial elongation has been linked to reduced scleral collagen fiber strength [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. With advancements in anterior segment imaging and biometry, increasing attention has been directed toward the relationship between the entire ocular structure, including the AL, and KC pathogenesis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough previous studies focused on direct correlations between the AL and corneal thickness, our study found that this link is weak (r\u0026thinsp;=\u0026thinsp;0.06\u0026ndash;0.08). Notably, the AL differed significantly across disease severity strata, with shorter AL observed in patients with more severe KC (higher Kmax and thinner TCT). This finding is consistent with that of a large population-based study published in 2023, which reported shorter AL as a significant risk factor for KC prevalence [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Our study is the first to report a correlation between the severity of KC and AL. These results suggests that the AL may influence KC severity indirectly through alterations in the biomechanical environment of the eye rather than through direct effects on corneal thickness, thereby providing a new target for clinical intervention strategies. Patients with similar KC severity but shorter AL may signify a higher risk of progression, warranting closer monitoring.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003ePredictive Value of Corneal Epithelial Thickness Variation\u003c/h2\u003e \u003cp\u003eThis study is the first to report a very strong negative correlation between the min-max epithelial thickness difference and Kmax (r = -0.83), which is significantly stronger than that observed for traditional parameters (e.g., TCT vs. Kmax, r \u0026asymp; -0.7). This finding indicates that epithelial thickness heterogeneity (degree of variation) may be a more sensitive marker of ectatic severity than absolute thickness values alone.\u003c/p\u003e \u003cp\u003eThe outermost protective layer of the corneal epithelium plays a crucial role in maintaining corneal biomechanical stability [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. During KC progression, the epithelium thins over the apex of the cone owing to mechanical stretching, accompanied by compensatory thickening in the periphery, resulting in an increased min\u0026ndash;max difference. This change in the thickness variation often precedes significant alterations in the corneal stroma, serving as a \"sensitive signal\" for early disease progression [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Compared with traditional parameters, such as Kmax and TCT, the min\u0026ndash;max difference is a noninvasive and more sensitive metric, making it a promising metric for early screening, disease monitoring, and postoperative follow-up, particularly in adolescent patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eBidirectional Regulatory Relationship Between IOP and Corneal Parameters\u003c/h2\u003e \u003cp\u003eOur study confirmed a strong negative correlation between NCT and Kmax and a strong positive correlation between NCT and TCT, highlighting the complex interaction between IOP measurement corneal biomechanics in KC. Corneal thinning and biomechanical weakening in KC result in systematic underestimation of the IOP. The American Academy of Ophthalmology 2024 Clinical Practice Guidelines for Corneal Ectasia state that IOP measurements using applanation tonometers (e.g., Goldmann) are artificially low in ectatic diseases owing to tissue thinning and biomechanical weakening. The guidelines recommend using alternative devices that are less dependent on corneal regularity, such as pneumatic, thickness-compensating, dynamic contour, or rebound tonometers and emphasize the loss of corneal resistance when interpreting IOP readings. A 2023 study also found that NCT measurements increased significantly after corneal crosslinking, an effect that was attributed to increased corneal stiffness [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Taken together, these findings emphasize that accurate IOP assessment in patients with KC requires consideration of corneal biomechanical properties, and advanced approaches such as biomechanically corrected IOP measurements using Corvis ST may offer superior clinical utility.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eKC in the Chinese population presents is characterized by adolescent clustering and a tendency towards initial unilateral presentation. A shorter axial length may be associated with an increased risk of disease progression. The min-max corneal epithelial thickness difference represents a highly sensitive indicator of disease severity. Future studies should further explore the influence of genetic and environmental factors on disease progression to inform optimized prevention and control strategies. Large-scale, multicenter studies incorporating genetic analyses and environmental exposure assessments are warranted to achieve a comprehensive understanding of the pathogenesis and progression of KC. Such efforts may provide a robust scientific foundation for precise diagnosis and personalized treatment, thereby supporting improved ocular health outcomes in the Chinese population.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eACT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eapical corneal thickness\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eaxial length\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIOP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintraocular pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ekeratoconus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKmax\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emaximum keratometry\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enon-contact tonometry\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ethinnest corneal thickness\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e \u003cp\u003e This retrospective study was approved by the ethics committee of the Eye and ENT Hospital affiliated with the Fudan Institutional Review Board (ethical code 2021118-1 ). This study was conducted according to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants after a detailed explanation of the study design.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for Publication\u003c/strong\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eDisclosure\u003c/h2\u003e \u003cp\u003eThe funders had no role in the study design, data collection and analysis, decision to publish, or manuscript preparation.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis work was supported by the National Key Research and Development Program of China (Grant No. 2023YFA0915000), Key Project of the Regional Innovation and Development Joint Fund of the National Natural Science Foundation of China (Grant No. U24A20708), Zhi Xing Shi Jie - Ophthalmic Clinical Research Support Project (Grant No.BFC-KECS-LC-20251022-03), and Shanghai Engineering Research Center of Laser and Autostereoscopic 3D for Vision Care (20DZ2255000).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eStudy concept and design (LL, LJ, CYG, XYZ,); data collection (LL, LJ, YLD, JT); data analysis and interpretation (LL, XYZ); drafting of the manuscript (LL, LJ); critical revision of the manuscript (XYZ, CYG,); supervision (XTZ, CYG, XYZ). All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data used in this study are available from the corresponding author upon request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSriranganathan A, Chan CC, Dhillon J, Felfeli T. Global Incidence and Prevalence of Keratoconus: A Systematic Review and Meta-Analysis. Cornea. 2025 Aug 20. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/ICO.0000000000003973\u003c/span\u003e\u003cspan address=\"10.1097/ICO.0000000000003973\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub ahead of print. PMID: 40833011.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Azevedo Magalh\u0026atilde;es O, Gon\u0026ccedil;alves MC, Gatinel D. The role of environment in the pathogenesis of keratoconus. 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Int Ophthalmol. 2023;43(12):4837\u0026ndash;49. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10792-023-02886-w\u003c/span\u003e\u003cspan address=\"10.1007/s10792-023-02886-w\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2023 Oct 20. PMID: 37861937; PMCID: PMC10724307.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"keratoconus, axial length, corneal epithelial thickness variation, predictive indicator","lastPublishedDoi":"10.21203/rs.3.rs-8952134/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8952134/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eKeratoconus (KC) is a bilateral, progressive, and non-inflammatory corneal ectatic disorder. This study aimed to characterize disease-specific features of KC in a Chinese population and analyze correlations among multidimensional clinical parameters using a large-scale clinical dataset, to support precision clinical screening and personalized treatment strategies.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eClinical records of 1,219 patients with KC treated between January 2019 and December 2023 were retrospectively analyzed. Collected variables included demographic characteristics, axial length (AL), intraocular pressure, and corneal parameters, including morphology and epithelial thickness. Statistical analyses were performed using SPSS version 26.0. Pearson\u0026rsquo;s correlation analysis was used to assess linear relationships between continuous variables, while one-way analysis of variance followed by Tukey\u0026rsquo;s honest significant difference post-hoc test were used to compare differences among the KC severity groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe mean patient age was 22.32\u0026thinsp;\u0026plusmn;\u0026thinsp;6.65 years, with adolescents and young adults accounting for more than 80% of the cohort. Unilateral surgery was performed in 90.0% of the cases, with a median interval of 17 days between bilateral procedures. The thinnest corneal point was predominantly located inferotemporally (right eye mean vector: 0.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22; left eye mean vector: 0.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26). The AL was significantly shorter in the maximum keratometry (Kmax)\u0026thinsp;\u0026ge;\u0026thinsp;58 D group than in the Kmax\u0026thinsp;\u0026lt;\u0026thinsp;48 D group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The AL was significantly longer in the thinnest corneal thickness (TCT)\u0026thinsp;\u0026gt;\u0026thinsp;490 \u0026micro;m group than in the groups with TCT\u0026thinsp;\u0026lt;\u0026thinsp;490 \u0026micro;m (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Non-contact tonometry exhibited a strong negative correlation with Kmax (r = -0.7) and a strong positive correlation with the TCT (r\u0026thinsp;=\u0026thinsp;0.61). Among epithelial parameters, the difference between the minimum and maximum corneal epithelial thickness demonstrated the strongest correlation with Kmax (r = -0.83).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eKC in the Chinese population is characterized by a marked clustering in adolescence and a tendency toward initial unilateral presentation. Shorter AL may be associated with an increased risk of severe disease. Corneal epithelial thickness variation, particularly the minimum\u0026ndash;maximum difference, serves as a highly sensitive indicator of KC severity, offering valuable insights for the development of precision screening and early intervention strategies.\u003c/p\u003e","manuscriptTitle":"Correlative Characteristics of Multidimensional Clinical Parameters and Predictive Value of Epithelial Thickness Variation in Chinese Patients with Keratoconus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-27 12:25:39","doi":"10.21203/rs.3.rs-8952134/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"489a7ee7-eea4-4987-a43b-5d1a1e0c79f7","owner":[],"postedDate":"March 27th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Withdrawn","date":"2026-05-06T15:32:24+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T15:41:33+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-27 12:25:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8952134","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8952134","identity":"rs-8952134","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}