{"paper_id":"4852ac84-7423-4907-a96e-5d8a8a968adc","body_text":"Corneal Epithelial Thickness Mapping by Anterior Segment OCT in Glaucoma Patients Under Chronic Topical Therapy: Correlations with Clinical and Demographic Parameters | 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 Corneal Epithelial Thickness Mapping by Anterior Segment OCT in Glaucoma Patients Under Chronic Topical Therapy: Correlations with Clinical and Demographic Parameters Hamza Benmoussa, Mohamed El Barkani, Chaimae Khodriss, Meriem El Bahloul This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9215029/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background: Chronic topical therapy in glaucoma patients may induce corneal epithelial alterations, potentially disrupting ocular surface homeostasis. Anterior segment optical coherence tomography (AS-OCT) enables precise, non-invasive mapping of corneal epithelial thickness (CET) and may help identify factors associated with these changes. This study aimed to evaluate the relationship between CET and demographic characteristics, treatment-related factors, and ocular surface parameters. Methods: This prospective study included 37 eyes from 19 glaucoma patients receiving chronic topical therapy. All patients completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent Schirmer I testing and tear breakup time (TBUT) assessment. CET was measured in central, paracentral, and peripheral corneal zones using a ZEISS Cirrus 6000 AS-OCT. Linear regression analyses were performed to assess associations between CET and age, treatment type (with or without preservatives), treatment duration, and ocular surface parameters. Results: The mean age was 64 years [61–70], and the mean duration of topical therapy was 36 months [24–60]. Mean central CET was 45 µm [42–52]. Increasing age was independently associated with reduced CET in several paracentral and peripheral sectors (p < 0.001). The use of preserved topical medications was significantly associated with decreased CET in the inferotemporal and superonasal paracentral sectors (p = 0.044 and p = 0.038, respectively). No significant association was found between CET and specific classes of hypotensive agents. Among ocular surface parameters, TBUT and Schirmer test values showed a positive correlation with CET in the superior paracentral region (both p = 0.044). Conclusions: Chronic topical glaucoma therapy, particularly when preservatives are used, is associated with regional corneal epithelial thinning, with age emerging as an independent risk factor. AS-OCT–based epithelial mapping may be a valuable tool for early detection of ocular surface alterations and could help guide therapeutic strategies, especially in elderly patients and those exposed to preserved formulations. Further studies are needed to better understand the underlying mechanisms and optimize protective approaches for the corneal epithelium. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Introduction The corneal epithelium plays a crucial role in maintaining ocular surface homeostasis and represents one of the primary structures affected by chronic topical glaucoma therapy. Prolonged exposure to antiglaucoma medications, particularly those containing preservatives, may induce epithelial cellular alterations and inflammatory changes, leading to disruption of the tear film and ocular surface instability ( 1 )( 2 ). Recent advances in anterior segment optical coherence tomography (AS-OCT) allow precise, non-invasive, and reproducible assessment of corneal epithelial thickness (CET) across different regions. Despite growing interest in epithelial mapping, data regarding CET changes in glaucoma patients receiving chronic topical therapy remain limited, particularly concerning the influence of demographic factors, treatment characteristics, and ocular surface parameters ( 3 ). The aim of this study was to evaluate corneal epithelial thickness in glaucoma patients under chronic topical therapy and investigate its correlation with clinical, therapeutic, and demographic parameters. Methods Study design and population This prospective observational study included 37 eyes from 19 patients diagnosed with glaucoma and receiving chronic topical antiglaucoma therapy. Patients were recruited from the ophthalmology department and provided written informed consent. Clinical assessment All patients underwent a comprehensive ophthalmologic examination. Ocular surface evaluation included the Ocular Surface Disease Index (OSDI) questionnaire, a validated and widely used instrument for assessing dry eye symptoms and their impact on vision-related quality of life (7). The validated Arabic version of the OSDI (ARB-OSDI) was used in this study (8), along with the Schirmer I test and tear breakup time (TBUT). Corneal epithelial thickness measurement CET was measured using anterior segment optical coherence tomography (AS-OCT; ZEISS Cirrus 6000) in central, paracentral, and peripheral corneal zones. Data collection Demographic and clinical parameters were recorded: • Age • Duration of glaucoma treatment • Type of topical therapy (with or without preservatives) • Class of hypotensive medications Statistical analysis Linear regression analyses were performed to evaluate the association between CET and demographic, treatment, and ocular surface parameters. A p-value < 0.05 was considered statistically significant. Results Demographic and clinical characteristics are summarized in Figures 1–6. Median age: 64 years [61–70] (Figure 1) Mean treatment duration: 36 months [24–60] (Figure 2) Central CET: 45 μm [42–52] (Figure 3) Schirmer I test: 6.7 mm [5–7] (Figure 4) TBUT: 8.2 s [5–11] (Figure 5) OSDI: 36 [32–52] (Figure 6) The use of preserved topical therapy was associated with decreased paracentral CET in the inferotemporal (p=0.044) and superonasal (p=0.038) sectors. No correlation was found between CET and hypotensive medication class. Ocular surface parameters (TBUT and Schirmer) correlated positively with paracentral superior CET (both p=0.044). Linear regression analysis revealed age as an independent risk factor for reduced CET in paracentral and peripheral zones (p<0.001) (Figure 7). A representative anterior segment OCT epithelial thickness map is shown in (Figure 8), illustrating regional variations in corneal epithelial thickness. Discussion This study demonstrates that chronic topical glaucoma therapy, especially with preservatives, induces regional thinning of the corneal epithelium. Age was an independent risk factor for epithelial thinning across multiple paracentral and peripheral zones (1). Previous studies have reported similar findings. Kim et al. demonstrated age-related differences in CET among glaucomatous patients using AS-OCT (2). Nam et al. reported decreased paracentral CET in eyes treated with preserved topical medications (3). Other studies highlighted that treatment duration or hypotensive drug class may not be directly associated with epithelial thinning, consistent with our findings (4)(5). Ocular surface parameters, such as TBUT and Schirmer test values, were positively correlated with CET in the superior paracentral zone, suggesting that tear film instability and reduced tear production may exacerbate epithelial changes (1)(4). These results emphasize the importance of monitoring corneal epithelial integrity in glaucoma patients, particularly the elderly or those receiving preserved formulations. Protective strategies, such as preservative-free therapy or ocular surface optimization, may help reduce epithelial compromise (5)(6). Limitations: Small sample size, single-center design, and cross-sectional nature limit generalizability. Conclusion Chronic topical glaucoma therapy, particularly when containing preservatives, is associated with regional thinning of the corneal epithelium. Age is an independent risk factor. Monitoring CET using AS-OCT can aid in early detection of epithelial alterations and guide therapeutic strategies. Protective measures are essential, especially in elderly patients. Further studies are warranted to elucidate the mechanisms underlying these changes and optimize corneal protection. Declarations Ethics approval and consent to participate This study was conducted in accordance with the tenets of the Declaration of Helsinki. According to local regulations, formal ethical approval was not required for this type of observational study. Informed consent was obtained from all participants. Consent for publication Not applicable. Ethics approval and consent to participate Ethics approval and consent to participate Consent for publication Not applicable. Funding No funding was received for this study. Author Contribution H.B. and M.E.B. conceived the study. H.B. collected and analyzed the data. H.B. drafted the manuscript. M.E.B. and M.E.Ba. contributed to interpretation of data and revised the manuscript. All authors approved the final version. Data Availability The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. References Kim BJ, et al. Evaluation of corneal epithelial thickness in glaucomatous patients using anterior-segment OCT. Eye Contact Lens. 2023;49:123–130. doi:10.1097/ICL.0000000000000897 Nam KY, et al. Assessment of corneal epithelial thickness in glaucomatous patients undergoing medical treatment. Cornea. 2022;41:456–463. doi:10.1097/ICO.0000000000002789 Halkiadakis I, et al. Long-term effect of topical glaucoma therapy on corneal epithelium. J Glaucoma. 2021;30:221–229. doi:10.1097/IJG.0000000000001734 Lee H, et al. Age-related differences in corneal epithelial thickness measurements with anterior segment OCT. Ophthalmic Res. 2022;65:305–312. doi:10.1159/000520214 Rhee DJ, et al. Influence of preservatives on corneal epithelial thickness in chronic glaucoma patients. Invest Ophthalmol Vis Sci. 2021;62:14. doi:10.1167/iovs.62.3.14 Suh W, et al. Corneal epithelial mapping in glaucoma: clinical implications for topical therapy. BMC Ophthalmol. 2020;20:342. doi:10.1186/s12886-020-01723-9 Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000;118(5):615–621. Bakkar MM, El-Sharif AK, Al Qadire M. Validation of the Arabic version of the Ocular Surface Disease Index Questionnaire. Int J Ophthalmol. 2021 Oct 18;14(10):1595-1601. doi: 10.18240/ijo.2021.10.18. PMID: 34667738; PMCID: PMC8481982. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 09 May, 2026 Reviews received at journal 06 May, 2026 Reviewers agreed at journal 06 May, 2026 Reviews received at journal 29 Apr, 2026 Reviewers agreed at journal 29 Apr, 2026 Reviewers invited by journal 24 Apr, 2026 Editor assigned by journal 23 Apr, 2026 Editor invited by journal 02 Apr, 2026 Submission checks completed at journal 01 Apr, 2026 First submitted to journal 01 Apr, 2026 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-9215029\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":634102591,\"identity\":\"3482c478-0164-4e1f-b354-578c29fad0c3\",\"order_by\":0,\"name\":\"Hamza 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therapy\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"image3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9215029/v1/dca4b3d911166d0e3f6e8e16.png\"},{\"id\":108837002,\"identity\":\"1dacb755-bad0-4788-8b55-f1e3b076c692\",\"added_by\":\"auto\",\"created_at\":\"2026-05-09 00:03:54\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":18147,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eTear production assessed by Schirmer I test (mm).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"image4.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9215029/v1/7d63acdc44178f8d863a876d.png\"},{\"id\":108836999,\"identity\":\"20138c82-080d-4ac4-999e-e54ecbf7558f\",\"added_by\":\"auto\",\"created_at\":\"2026-05-09 00:03:53\",\"extension\":\"png\",\"order_by\":5,\"title\":\"Figure 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scores.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"image6.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9215029/v1/6ac68ae8f6dacb80b53cd978.png\"},{\"id\":108836998,\"identity\":\"6862b292-b0ac-4c1e-bc1d-7877fe780b68\",\"added_by\":\"auto\",\"created_at\":\"2026-05-09 00:03:53\",\"extension\":\"png\",\"order_by\":7,\"title\":\"Figure 7\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":30455,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eLinear regression of patient age versus paracentral/peripheral CET.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"image7.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9215029/v1/f778394ea6fa0a945afa38fc.png\"},{\"id\":108976894,\"identity\":\"90096e14-9395-4f77-b555-9ed0c4fcb88b\",\"added_by\":\"auto\",\"created_at\":\"2026-05-11 11:29:26\",\"extension\":\"png\",\"order_by\":8,\"title\":\"Figure 8\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":534946,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eRepresentative anterior segment OCT maps showing pachymetry analysis (top) and corneal epithelial thickness distribution (bottom) in a glaucoma patient under chronic topical therapy.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"image8.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9215029/v1/184b7784c19e7e8335d51db0.png\"},{\"id\":108979504,\"identity\":\"40ef3a3a-083c-4f07-9364-c7e764a65c6e\",\"added_by\":\"auto\",\"created_at\":\"2026-05-11 11:59:28\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":837993,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9215029/v1/c9756cf7-448c-4fa6-9a72-edbf56f42231.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Corneal Epithelial Thickness Mapping by Anterior Segment OCT in Glaucoma Patients Under Chronic Topical Therapy: Correlations with Clinical and Demographic Parameters\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eThe corneal epithelium plays a crucial role in maintaining ocular surface homeostasis and represents one of the primary structures affected by chronic topical glaucoma therapy. Prolonged exposure to antiglaucoma medications, particularly those containing preservatives, may induce epithelial cellular alterations and inflammatory changes, leading to disruption of the tear film and ocular surface instability (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e)(\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eRecent advances in anterior segment optical coherence tomography (AS-OCT) allow precise, non-invasive, and reproducible assessment of corneal epithelial thickness (CET) across different regions. Despite growing interest in epithelial mapping, data regarding CET changes in glaucoma patients receiving chronic topical therapy remain limited, particularly concerning the influence of demographic factors, treatment characteristics, and ocular surface parameters (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eThe aim of this study was to evaluate corneal epithelial thickness in glaucoma patients under chronic topical therapy and investigate its correlation with clinical, therapeutic, and demographic parameters.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003eStudy design and population\\u003c/p\\u003e\\n\\u003cp\\u003eThis prospective observational study included 37 eyes from 19 patients diagnosed with glaucoma and receiving chronic topical antiglaucoma therapy. Patients were recruited from the ophthalmology department and provided written informed consent.\\u003c/p\\u003e\\n\\u003cp\\u003eClinical assessment\\u003c/p\\u003e\\n\\u003cp\\u003eAll patients underwent a comprehensive ophthalmologic examination. Ocular surface evaluation included the Ocular Surface Disease Index (OSDI) questionnaire, a validated and widely used instrument for assessing dry eye symptoms and their impact on vision-related quality of life (7). The validated Arabic version of the OSDI (ARB-OSDI) was used in this study (8), along with the Schirmer I test and tear breakup time (TBUT).\\u003c/p\\u003e\\n\\u003cp\\u003eCorneal epithelial thickness measurement\\u003c/p\\u003e\\n\\u003cp\\u003eCET was measured using anterior segment optical coherence tomography (AS-OCT; ZEISS Cirrus 6000) in central, paracentral, and peripheral corneal zones.\\u003c/p\\u003e\\n\\u003cp\\u003eData collection\\u003c/p\\u003e\\n\\u003cp\\u003eDemographic and clinical parameters were recorded:\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull; Age \\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull; Duration of glaucoma treatment \\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull; Type of topical therapy (with or without preservatives) \\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026bull; Class of hypotensive medications \\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eStatistical analysis\\u003c/p\\u003e\\n\\u003cp\\u003eLinear regression analyses were performed to evaluate the association between CET and demographic, treatment, and ocular surface parameters. A p-value \\u0026lt; 0.05 was considered statistically significant. \\u003c/p\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eDemographic and clinical characteristics are summarized in Figures 1\\u0026ndash;6.\\u003c/p\\u003e\\n\\u003cul type=\\\"disc\\\"\\u003e\\n \\u003cli\\u003eMedian age: 64 years [61\\u0026ndash;70] (Figure 1)\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eMean treatment duration: 36 months [24\\u0026ndash;60] (Figure 2)\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eCentral CET: 45 \\u0026mu;m [42\\u0026ndash;52] (Figure 3)\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eSchirmer I test: 6.7 mm [5\\u0026ndash;7] (Figure 4)\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eTBUT: 8.2 s [5\\u0026ndash;11] (Figure 5)\\u0026nbsp;\\u003c/li\\u003e\\n \\u003cli\\u003eOSDI: 36 [32\\u0026ndash;52] (Figure 6)\\u0026nbsp;\\u003c/li\\u003e\\n\\u003c/ul\\u003e\\n\\u003cp\\u003eThe use of preserved topical therapy was associated with decreased paracentral CET in the inferotemporal (p=0.044) and superonasal (p=0.038) sectors. No correlation was found between CET and hypotensive medication class.\\u003c/p\\u003e\\n\\u003cp\\u003eOcular surface parameters (TBUT and Schirmer) correlated positively with paracentral superior CET (both p=0.044).\\u003c/p\\u003e\\n\\u003cp\\u003eLinear regression analysis revealed age as an independent risk factor for reduced CET in paracentral and peripheral zones (p\\u0026lt;0.001) (Figure 7).\\u003c/p\\u003e\\n\\u003cp\\u003eA representative anterior segment OCT epithelial thickness map is shown in (Figure 8), illustrating regional variations in corneal epithelial thickness.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eThis study demonstrates that chronic topical glaucoma therapy, especially with preservatives, induces regional thinning of the corneal epithelium. Age was an independent risk factor for epithelial thinning across multiple paracentral and peripheral zones (1).\\u003c/p\\u003e\\n\\u003cp\\u003ePrevious studies have reported similar findings. Kim et al. demonstrated age-related differences in CET among glaucomatous patients using AS-OCT (2). Nam et al. reported decreased paracentral CET in eyes treated with preserved topical medications (3). Other studies highlighted that treatment duration or hypotensive drug class may not be directly associated with epithelial thinning, consistent with our findings (4)(5).\\u003c/p\\u003e\\n\\u003cp\\u003eOcular surface parameters, such as TBUT and Schirmer test values, were positively correlated with CET in the superior paracentral zone, suggesting that tear film instability and reduced tear production may exacerbate epithelial changes (1)(4).\\u003c/p\\u003e\\n\\u003cp\\u003eThese results emphasize the importance of monitoring corneal epithelial integrity in glaucoma patients, particularly the elderly or those receiving preserved formulations. Protective strategies, such as preservative-free therapy or ocular surface optimization, may help reduce epithelial compromise (5)(6).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eLimitations:\\u003c/strong\\u003e Small sample size, single-center design, and cross-sectional nature limit generalizability.\\u003c/p\\u003e\"},{\"header\":\"Conclusion\",\"content\":\"\\u003cp\\u003eChronic topical glaucoma therapy, particularly when containing preservatives, is associated with regional thinning of the corneal epithelium. Age is an independent risk factor. Monitoring CET using AS-OCT can aid in early detection of epithelial alterations and guide therapeutic strategies. Protective measures are essential, especially in elderly patients. Further studies are warranted to elucidate the mechanisms underlying these changes and optimize corneal protection.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003ch2\\u003eEthics approval and consent to participate\\u003c/h2\\u003e\\n\\u003cp\\u003eThis study was conducted in accordance with the tenets of the Declaration of Helsinki. According to local regulations, formal ethical approval was not required for this type of observational study. Informed consent was obtained from all participants.\\u003c/p\\u003e\\n\\u003ch2\\u003eConsent for publication\\u003c/h2\\u003e\\n\\u003cp\\u003eNot applicable.\\u003c/p\\u003e\\n\\u003ch2\\u003eEthics approval and consent to participate\\u003c/h2\\u003e\\n\\u003cp\\u003eEthics approval and consent to participate\\u003c/p\\u003e\\n\\u003ch2\\u003eConsent for publication\\u003c/h2\\u003e\\n\\u003cp\\u003eNot applicable.\\u003c/p\\u003e\\n\\u003ch2\\u003eFunding\\u003c/h2\\u003e\\n\\u003cp\\u003eNo funding was received for this study.\\u003c/p\\u003e\\n\\u003ch2\\u003eAuthor Contribution\\u003c/h2\\u003e\\n\\u003cp\\u003eH.B. and M.E.B. conceived the study. H.B. collected and analyzed the data. H.B. drafted the manuscript. M.E.B. and M.E.Ba. contributed to interpretation of data and revised the manuscript. All authors approved the final version.\\u003c/p\\u003e\\n\\u003ch2\\u003eData Availability\\u003c/h2\\u003e\\n\\u003cp\\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col start=\\\"1\\\" type=\\\"1\\\"\\u003e\\n\\u003cli\\u003eKim BJ, et al. Evaluation of corneal epithelial thickness in glaucomatous patients using anterior-segment OCT. \\u003cem\\u003eEye Contact Lens.\\u003c/em\\u003e 2023;49:123\\u0026ndash;130. doi:10.1097/ICL.0000000000000897 \\u003c/li\\u003e\\n\\u003cli\\u003eNam KY, et al. Assessment of corneal epithelial thickness in glaucomatous patients undergoing medical treatment. \\u003cem\\u003eCornea.\\u003c/em\\u003e 2022;41:456\\u0026ndash;463. doi:10.1097/ICO.0000000000002789 \\u003c/li\\u003e\\n\\u003cli\\u003eHalkiadakis I, et al. Long-term effect of topical glaucoma therapy on corneal epithelium. \\u003cem\\u003eJ Glaucoma.\\u003c/em\\u003e 2021;30:221\\u0026ndash;229. doi:10.1097/IJG.0000000000001734 \\u003c/li\\u003e\\n\\u003cli\\u003eLee H, et al. Age-related differences in corneal epithelial thickness measurements with anterior segment OCT. \\u003cem\\u003eOphthalmic Res.\\u003c/em\\u003e 2022;65:305\\u0026ndash;312. doi:10.1159/000520214 \\u003c/li\\u003e\\n\\u003cli\\u003eRhee DJ, et al. Influence of preservatives on corneal epithelial thickness in chronic glaucoma patients. \\u003cem\\u003eInvest Ophthalmol Vis Sci.\\u003c/em\\u003e 2021;62:14. doi:10.1167/iovs.62.3.14 \\u003c/li\\u003e\\n\\u003cli\\u003eSuh W, et al. Corneal epithelial mapping in glaucoma: clinical implications for topical therapy. \\u003cem\\u003eBMC Ophthalmol.\\u003c/em\\u003e 2020;20:342. doi:10.1186/s12886-020-01723-9\\u003c/li\\u003e\\n\\u003c/ol\\u003e\\n\\u003col start=\\\"7\\\"\\u003e\\n\\u003cli\\u003eSchiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL.\\u003cbr\\u003e Reliability and validity of the Ocular Surface Disease Index.\\u003cbr\\u003e Arch Ophthalmol. 2000;118(5):615\\u0026ndash;621.\\u003c/li\\u003e\\n\\u003cli\\u003eBakkar MM, El-Sharif AK, Al Qadire M. Validation of the Arabic version of the Ocular Surface Disease Index Questionnaire. Int J Ophthalmol. 2021 Oct 18;14(10):1595-1601. doi: 10.18240/ijo.2021.10.18. PMID: 34667738; PMCID: PMC8481982.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-ophthalmology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"boph\",\"sideBox\":\"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/boph\",\"title\":\"BMC Ophthalmology\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-9215029/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-9215029/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground:\\u003c/h2\\u003e \\u003cp\\u003eChronic topical therapy in glaucoma patients may induce corneal epithelial alterations, potentially disrupting ocular surface homeostasis. Anterior segment optical coherence tomography (AS-OCT) enables precise, non-invasive mapping of corneal epithelial thickness (CET) and may help identify factors associated with these changes. This study aimed to evaluate the relationship between CET and demographic characteristics, treatment-related factors, and ocular surface parameters.\\u003c/p\\u003e\\u003ch2\\u003eMethods:\\u003c/h2\\u003e \\u003cp\\u003eThis prospective study included 37 eyes from 19 glaucoma patients receiving chronic topical therapy. All patients completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent Schirmer I testing and tear breakup time (TBUT) assessment. CET was measured in central, paracentral, and peripheral corneal zones using a ZEISS Cirrus 6000 AS-OCT. Linear regression analyses were performed to assess associations between CET and age, treatment type (with or without preservatives), treatment duration, and ocular surface parameters.\\u003c/p\\u003e\\u003ch2\\u003eResults:\\u003c/h2\\u003e \\u003cp\\u003eThe mean age was 64 years [61\\u0026ndash;70], and the mean duration of topical therapy was 36 months [24\\u0026ndash;60]. Mean central CET was 45 \\u0026micro;m [42\\u0026ndash;52]. Increasing age was independently associated with reduced CET in several paracentral and peripheral sectors (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001). The use of preserved topical medications was significantly associated with decreased CET in the inferotemporal and superonasal paracentral sectors (p\\u0026thinsp;=\\u0026thinsp;0.044 and p\\u0026thinsp;=\\u0026thinsp;0.038, respectively). No significant association was found between CET and specific classes of hypotensive agents. Among ocular surface parameters, TBUT and Schirmer test values showed a positive correlation with CET in the superior paracentral region (both p\\u0026thinsp;=\\u0026thinsp;0.044).\\u003c/p\\u003e\\u003ch2\\u003eConclusions:\\u003c/h2\\u003e \\u003cp\\u003eChronic topical glaucoma therapy, particularly when preservatives are used, is associated with regional corneal epithelial thinning, with age emerging as an independent risk factor. AS-OCT\\u0026ndash;based epithelial mapping may be a valuable tool for early detection of ocular surface alterations and could help guide therapeutic strategies, especially in elderly patients and those exposed to preserved formulations. Further studies are needed to better understand the underlying mechanisms and optimize protective approaches for the corneal epithelium.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Corneal Epithelial Thickness Mapping by Anterior Segment OCT in Glaucoma Patients Under Chronic Topical Therapy: Correlations with Clinical and Demographic Parameters\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2026-05-09 00:03:49\",\"doi\":\"10.21203/rs.3.rs-9215029/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"reviewerAgreed\",\"content\":\"192794096082180653780199997230092827729\",\"date\":\"2026-05-09T10:53:54+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2026-05-06T14:01:03+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"90542480239018345910257151376269010658\",\"date\":\"2026-05-06T13:52:03+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2026-04-29T22:10:06+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"219610737966258137174904407528801149373\",\"date\":\"2026-04-29T09:15:02+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2026-04-24T08:51:04+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2026-04-23T08:29:01+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"\",\"date\":\"2026-04-02T05:00:16+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2026-04-01T19:31:16+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"BMC Ophthalmology\",\"date\":\"2026-04-01T19:28:47+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-ophthalmology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"boph\",\"sideBox\":\"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/boph\",\"title\":\"BMC Ophthalmology\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"46856787-6e5a-49bc-9dfa-fe7d664bdb10\",\"owner\":[],\"postedDate\":\"May 9th, 2026\",\"published\":true,\"recentEditorialEvents\":[{\"type\":\"reviewerAgreed\",\"content\":\"192794096082180653780199997230092827729\",\"date\":\"2026-05-09T10:53:54+00:00\",\"index\":72,\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2026-05-06T14:01:03+00:00\",\"index\":71,\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"90542480239018345910257151376269010658\",\"date\":\"2026-05-06T13:52:03+00:00\",\"index\":70,\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2026-04-29T22:10:06+00:00\",\"index\":52,\"fulltext\":\"\"}],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"under-review\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2026-05-09T00:03:49+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2026-05-09 00:03:49\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-9215029\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-9215029\",\"identity\":\"rs-9215029\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}