Glycated hemoglobin as a continuous metabolic determinant of intraocular pressure independent of diabetic status: a prospective observational study in Kosovo

Glycated hemoglobin as a continuous metabolic determinant of intraocular pressure independent of diabetic status: a prospective observational study in Kosovo | 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 Glycated hemoglobin as a continuous metabolic determinant of intraocular pressure independent of diabetic status: a prospective observational study in Kosovo Agon Rrusta, Gazmend Kacaniku, Ali Tonuzi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8575724/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 Elevated intraocular pressure (IOP) has been associated with diabetes mellitus; however, the role of chronic hyperglycemia in both diabetic and non-diabetic patients remain a topic of exploration with regard to dysregulation of trabecular meshwork and humor aqueous drainage especially in understudied regions such as Kosovo and Southeast Europe. Objective To evaluate glycated hemoglobin (HbA1c) as a continuous metabolic determinant of intraocular pressure independent of diabetes mellitus diagnosis. Methods In this prospective observational study, 150 participants (100 with diabetes and 50 non-diabetic controls) were enrolled. HbA1c values obtained within three months of ocular examination were analyzed as a continuous variable. IOP was measured using applanation or non-contact tonometry. Associations between HbA1c and IOP were assessed using correlation and linear regression analyses. Results Mean IOP was significantly higher in diabetic participants compared with controls (p < 0.001). Across the entire cohort, HbA1c demonstrated a significant positive association with IOP, including within the non-diabetic range. Linear regression confirmed HbA1c as an independent predictor of IOP in both diabetic (R² = 0.10, p = 0.0011) and non-diabetic individuals (R² = 0.15, p = 0.0059). Conclusion Chronic hyperglycemia is associated with intraocular pressure across diabetic and non-diabetic populations, suggesting that chronic glycemic exposure may influence ocular physiology beyond conventional disease classifications. These findings support the consideration of metabolic glycemic status in glaucoma risk assessment in this population. Ophthalmology Diabetus Mellitus hyperglycemia intraocular pressure glaucoma diabetic retinopathy Figures Figure 1 Figure 2 Introduction What is already known Elevated intraocular pressure has been reported more frequently in individuals with diabetes, and hyperglycemia has been implicated in altered trabecular meshwork function. What this study adds This study demonstrates that HbA1c acts as a continuous metabolic determinant of intraocular pressure independent of diabetes diagnosis, extending the concept of glycemic influence to non-diabetic individuals. This is especially clinically relevant as it pertains to the population of Kosovo and in the region of Southeast Europe, a region that has been understudied in this topic. Diabetes mellitus is a major global public health concern, with prevalence projected to increase substantially in the coming decades [ 1 ]. There is limited data on the prevalence of Diabetes and Glaucoma in Kosovo as a developing country. This study aims to investigate the impact of hyperglycemia as associated with high intraocular pressure and glaucoma which is an underexplored association in Kosovo and in the region, with limited data. Epidemiologic studies indicate that patients with type 1 and type 2 diabetes are at higher risk of elevated intraocular pressure (IOP) and glaucoma [ 1 – 2 ]. Furthermore, individuals with long-standing, poorly controlled diabetes and related complications appear to be at particularly high risk for elevated IOP [ 2 – 3 ]. Experimental evidence from in vitro models suggests that chronic hyperglycemia can induce extracellular matrix deposition in the trabecular meshwork, potentially obstructing aqueous humor outflow [ 1 – 2 ]. This extracellular matrix accumulation may include fibronectin and glycosaminoglycans, both of which are implicated in impaired aqueous drainage and elevated IOP [ 3 – 4 ]. Glycated hemoglobin (HbA1c) is a widely accepted biomarker for assessing long-term glycemic control [ 1 – 3 ]. Unlike prior studies that examined intraocular pressure primarily in diabetic cohorts, this study evaluates HbA1c as a continuous metabolic marker influencing intraocular pressure in both diabetic and non-diabetic individuals, thereby exploring glycemic control as an independent modifier of IOP. Methods This prospective observational study was conducted at the University Clinical Center of Kosovo Eye Clinic and the Italian Eye Hospital in Prishtina, Kosovo between June 2022 and June 2024. The study was approved by the Ethical Commission of the University Clinical Center of Kosovo and the Faculty of Medicine at the University of Prishtina (Reference No. 4/291). Data on the association between HbA1c and intraocular pressure in Southeastern European diabetic and non-diabetic populations remain limited especially in a developing and new country such as Kosovo. All participants provided written informed consent prior to enrollment. The study adhered to the principles of the Declaration of Helsinki and complied with national regulations regarding the protection of personal data. A total of 200 patients were screened, and 150 were included in the final analysis: 100 with a confirmed diagnosis of type 1 or type 2 diabetes and 50 non-diabetic controls. Diabetic participants included individuals with non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR). HbA1c was analyzed as a continuous biological variable of chronic hyperglycemia rather than dichotomized by diabetic status to better reflect metabolic exposure. Demographic data, diabetes duration, smoking status, systemic comorbidities, and presence of diabetic retinopathy were recorded. HbA1c levels (measured within the preceding 3 months) were obtained from medical records; patients without recent results were instructed to obtain testing within 1 month, after which IOP was measured on the same day. IOP was measured using Goldmann applanation tonometry or non-contact pneumotonometry. Descriptive statistics were used to summarize demographic and clinical characteristics. Pearson correlation was used to evaluate the association between HbA1c and IOP. Between-group comparisons were performed using independent t tests. Linear regression analysis was used to model the relationship between HbA1c and IOP. A p value < 0.05 was considered statistically significant. Ethical Approval: The study was approved by the Ethical Commission of the University Clinical Center of Kosovo and the Faculty of Medicine at the University of Prishtina (reference No. 4/291). All participants provided written informed consent prior to enrollment. The study adhered to the principles of the Declaration of Helsinki and complied with national regulations regarding the protection of personal data. Results A total of 150 participants were enrolled (49% male, 51% female), including 100 with diabetes and 50 non-diabetic controls. The mean age was 63.8 years for the diabetic group and 56.5 years for the control group. The mean duration of diabetes in the diabetic cohort was 16 years. Mean IOP was significantly higher in the diabetic group compared with controls for both the right eye (OD: 17.07 mmHg vs 14.26 mmHg, p < 0.001) and the left eye (OS: 16.89 mmHg vs 14.36 mmHg, p < 0.001). Mean HbA1c was also significantly higher among diabetic participants (6.99%) than controls (5.55%, p < 0.001). The prevalence of diabetic retinopathy (NPDR or PDR) among diabetic patients was 70%. Hypertension was present in 49% of diabetics and 32% of controls. Smoking was reported by 35% of diabetics and 34% of controls. A scatter plot analysis demonstrated a positive association between HbA1c and IOP in both groups (Figure 1). Linear regression analysis confirmed statistical significance in both the control group (slope = 2.18, R² = 0.15, p = 0.0059) and the diabetic group (slope = 1.45, R² = 0.10, p = 0.0011). The coefficients of determination indicate that HbA1c accounts for a modest proportion of IOP variability. Discussion This study demonstrates that chronic glycemic exposure, reflected by HbA1c levels, is associated with intraocular pressure across individuals with and without diabetes, suggesting a metabolic influence on IOP that extends beyond traditional disease classifications. These findings suggest that hyperglycemia may play a role in ocular physiology beyond its established association with diabetic retinopathy and other diabetic ocular complications. Previous studies have reported a relationship between hyperglycemia and elevated IOP, although the underlying mechanisms remain incompletely understood [1-4]. Persistent hyperglycemia has been shown to induce histologic changes in the trabecular meshwork, including deposition of extracellular matrix components such as fibronectin and glycosaminoglycans, which may reduce aqueous humor outflow and contribute to IOP elevation [2-4]. Experimental work in animal models has demonstrated a two- to three-fold increase in aqueous humor glucose levels in diabetic compared with non-diabetic subjects, further supporting this mechanistic link [5-7]. These findings suggest that HbA1c may act as a metabolic modifier of intraocular pressure, potentially influencing clinical thresholds used for glaucoma risk assessment. Unlike prior studies that primarily compared diabetic and non-diabetic groups, the present study conceptualizes HbA1c as a continuous marker of metabolic exposure influencing intraocular pressure across the full glycemic and metabolic spectrum. The observed association within non-diabetic individuals suggests that even subclinical hyperglycemia may affect aqueous humor dynamics, supporting a metabolic rather than categorical disease model of IOP regulation The present study aligns with epidemiologic evidence from large-scale cohorts, including the Framingham Eye Study and the Rotterdam Study, which have reported higher prevalence of ocular hypertension and glaucoma among individuals with diabetes [6-8]. While the association in our study was statistically significant, the modest R² values suggest that HbA1c explains only part of the variability in IOP, indicating that additional factors—such as corneal thickness, ocular biomechanics, and systemic vascular health—also influence IOP regulation. From a clinical perspective, these findings highlight the importance of integrating glycemic assessment into routine ophthalmologic evaluations, particularly for patients at risk of glaucoma. Screening for elevated IOP in individuals with poor glycemic control could enable earlier intervention and potentially reduce the risk of optic nerve damage. Furthermore, chronic glycemic exposure may influence intraocular pressure through multiple mechanisms, including increased trabecular meshwork extracellular matrix deposition, altered corneal biomechanics, and changes in aqueous humor osmolarity. These processes are not exclusive to overt diabetes and may begin at HbA1c levels traditionally considered non-pathologic. Future studies incorporating central corneal thickness, corneal hysteresis, and longitudinal glycemic monitoring would further clarify the metabolic contribution to IOP regulation. Conclusion This study demonstrates a significant positive correlation between chronic hyperglycemia and intraocular pressure (IOP) in both diabetic and non-diabetic individuals. The consistent association across groups suggests that chronic hyperglycemia may contribute to IOP elevation, potentially increasing the risk of glaucomatous optic neuropathy. These findings support the integration of glycemic status assessment into routine ophthalmologic care, particularly for patients at elevated risk of glaucoma. Further longitudinal and mechanistic studies are warranted to determine whether improved glycemic control can reduce IOP and mitigate glaucoma risk. Declarations Acknowledgments: I would like to thank all my colleagues for providing administrative and material support. All authors have read and approved the manuscript. The manuscript and parts of it have not and will not be submitted elsewhere for publication. AI was used for checking of grammatical errors of the research paper. Financial disclosure: The authors have nothing to disclose and no financial interests to disclose. Conflicts of interest: Authors declare that they have no conflicts of interest. Data availability: The data that support the findings in this study are available from the corresponding author upon request. Key Points: - Novel finding : HbA1c acts as a continuous metabolic determinant of intraocular pressure independent of diabetes diagnosis. - Clinical implication: Elevated HbA1c may be a risk factor for increased IOP, independent of diabetes status. - Relevance: Supports the integration of glycemic assessment into routine eye examinations for early detection of ocular hypertension and glaucoma. - Research gap: Longitudinal studies are needed to clarify causality and evaluate the impact of glycemic control on IOP. - Public health perspective: Early detection and management of hyperglycemia may help prevent glaucoma-related vision loss. Ethical Approval: The study was approved by the Ethical Commission of the University Clinical Center of Kosovo and the Faculty of Medicine at the University of Prishtina (reference No. 4/291). All participants provided written informed consent prior to enrollment. The study adhered to the principles of the Declaration of Helsinki and complied with national regulations regarding the protection of personal data. Patient Consent: The authors want to specify that they have obtained a written signed patient consent for the use of their information and the data. All patients included in this study have given their informed consent in order for their clinical information and images to be used and reported in this publication. Declaration of Contribution: Dr.Agon Rrusta conceived and designed the study and collected the data. Dr.Agon Rrusta, Prof.asoc.Gazmend Kacaniku, Dr.Ferdije Brahimi, Dr.Shpat Rrusta, Dr.Dile Rrusta collected the data. Dr.Agon Rrusta and Prof.Gazmend Kacaniku performed the statistical analysis and drafted the manuscript. Prof.asoc. Gazmend Kacaniku and Prof.asoc Ali Tonuzi revised the manuscript. All authors read and approved the final version of the manuscript. References Hymowitz MB, Chang D, Feinberg EB, Roy S. Increased intraocular pressure and hyperglycemic level in diabetic patients. PLoS One. 2016;11(3):e0151833. doi:10.1371/journal.pone.0151833. Matsuoka M, Ogata N, Matsuyama K, Yoshikawa T, Takahashi K. Intraocular pressure in Japanese diabetic patients. Clin Ophthalmol. 2012;6:1005-1009. doi:10.2147/OPTH.S33131. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998;21(9):1414-1431. doi:10.2337/diacare.21.9.1414. Bacharach J, Delgado MF, Iwach AG. Comparison of the efficacy of the fixed-combination timolol/dorzolamide versus concomitant administration of timolol and dorzolamide. J Ocul Pharmacol Ther. 2003;19(2):93-96. doi:10.1089/108076803321636440. Klein BE, Klein R, Jensen SC. Open-angle glaucoma and older-onset diabetes: The Beaver Dam Eye Study. Ophthalmology. 1994;101(1):117-121. doi:10.1016/S0161-6420(94)31355-7. Oshitari T, Roy S. Effect of chronic hyperglycemia on intraocular pressure in patients with diabetes. Am J Ophthalmol. 2007;143(2):363-365. doi:10.1016/j.ajo.2006.09.030. Kahn HA, Milton RC. Revised Framingham Eye Study: prevalence of glaucoma and diabetic retinopathy. Am J Epidemiol. 1980;111(6):769-776. doi:10.1093/oxfordjournals.aje.a112954. Sato T, Roy S. Effect of high glucose on fibronectin expression and cell proliferation in trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2002;43(1):170-175. Rohen JW. Why is intraocular pressure elevated in chronic simple glaucoma? Anatomic considerations. Ophthalmology. 1983;90(7):758-765. doi:10.1016/S0161-6420(83)34520-2. Babizhayev MA, Brodskaya MW. Fibronectin detection in drainage outflow system of human eyes in ageing and progression of open-angle glaucoma. Mech Ageing Dev. 1989;47(2):145-157. doi:10.1016/0047-6374(89)90021-8. Perez-Rico C, Gutierrez-Ortiz C, Gonzalez-Mesa A, et al. Effect of diabetes mellitus on Corvis ST measurement process. Acta Ophthalmol. 2015;93(3):e193-e198. doi:10.1111/aos.12530. Rombold F, Thiel MJ, Neubauer AS, Hirneiss C, Kampik A. Evaluation of portable TGDc-01 tonometers and comparison with the Goldmann applanation tonometer. Ophthalmologe. 2005;102(2):158-162. doi:10.1007/s00347-004-1078-1. Dielemans I, de Jong PT, Stolk R, Vingerling JR, Grobbee DE, Hofman A. Primary open-angle glaucoma, intraocular pressure, and diabetes mellitus in the general elderly population: The Rotterdam Study. Ophthalmology. 1996;103(8):1271-1275. doi:10.1016/S0161-6420(96)30505-7. Lütjen-Drecoll E. Functional morphology of the trabecular meshwork in primate eyes. Prog Retin Eye Res. 1999;18(1):91-119. doi:10.1016/S1350-9462(98)00011-1. Braha A, Simion A, Timar R, Timar B. Factors Associated with Increased Intraocular Pressure in Type 2 Diabetes Patients. Journal of Clinical Medicine . 2024; 13(3):676. https://doi.org/10.3390/jcm13030676. Samal, A., Panda, L., Khan, Z. U., Dash, R. J., & Sahoo, K. K. (2021). Study of intraocular pressure in diabetes mellitus patients. International Journal of Science and Healthcare Research , 6 (1), 21-29. Pimentel LG, Gracitelli CP, da Silva LS, Souza AK, Prata TS. Association between Glucose Levels and Intraocular Pressure: Pre- and Postprandial Analysis in Diabetic and Nondiabetic Patients. J Ophthalmol. 2015;2015:832058. doi: 10.1155/2015/832058. Epub 2015 Jan 6. PMID: 25642344; PMCID: PMC4302384. Tables Table 1. Demographic and Clinical Characteristics of Study Participants Characteristic All Participants (n=150) Diabetes (n=100) Control (n=50) Age, mean (y) 63.8 56.5 Male sex, n (%) 40 (40) — Female sex, n (%) 60 (60) — Duration of diabetes, mean (y) 16 — IOP, mean (mmHg) OD 17.07 14.26 IOP, mean (mmHg) OS 16.89 14.36 HbA1c, mean (%) 6.99 5.55 Diabetic retinopathy, n (%) 70 (70) 0 (0) Hypertension, n (%) 49 (49) 16 (32) Smoking, n (%) 35 (35) 17 (34) Other systemic disorders, n (%) 41 (41) 4 (8) Type 1 diabetes, n (%) 20 (20) — Type 2 diabetes, n (%) 80 (80) — Table 2. Linear Regression Results for the Relationship Between HbA1c and IOP Group Slope Intercept r Value R² p Value Standard Error Control 2.18 1.83 0.388 0.15 0.0059 0.757 Diabetic 1.45 6.83 0.320 0.10 0.0011 0.431 Additional Declarations The authors declare no competing interests. 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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-8575724","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":572842634,"identity":"4e3bf3a9-ed72-45f6-b168-626bfcf18b10","order_by":0,"name":"Agon 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2","display":"","copyAsset":false,"role":"figure","size":46327,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMean IOP and SD by Group\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8575724/v1/d204efb4e7f5aa2e9d79870b.png"},{"id":100412351,"identity":"51cf9c42-140b-414e-b6d5-eef62ea17787","added_by":"auto","created_at":"2026-01-16 13:14:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":663567,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8575724/v1/1694fd3f-bb77-44e4-ab5a-3d02345eeff6.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eGlycated hemoglobin as a continuous metabolic determinant of intraocular pressure independent of diabetic status: a prospective observational study in Kosovo\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e \u003ch2\u003eWhat is already known\u003c/h2\u003e \u003cp\u003eElevated intraocular pressure has been reported more frequently in individuals with diabetes, and hyperglycemia has been implicated in altered trabecular meshwork function.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eWhat this study adds\u003c/h2\u003e \u003cp\u003eThis study demonstrates that HbA1c acts as a continuous metabolic determinant of intraocular pressure independent of diabetes diagnosis, extending the concept of glycemic influence to non-diabetic individuals. This is especially clinically relevant as it pertains to the population of Kosovo and in the region of Southeast Europe, a region that has been understudied in this topic.\u003c/p\u003e \u003cp\u003eDiabetes mellitus is a major global public health concern, with prevalence projected to increase substantially in the coming decades [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. There is limited data on the prevalence of Diabetes and Glaucoma in Kosovo as a developing country. This study aims to investigate the impact of hyperglycemia as associated with high intraocular pressure and glaucoma which is an underexplored association in Kosovo and in the region, with limited data. Epidemiologic studies indicate that patients with type 1 and type 2 diabetes are at higher risk of elevated intraocular pressure (IOP) and glaucoma [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Furthermore, individuals with long-standing, poorly controlled diabetes and related complications appear to be at particularly high risk for elevated IOP [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eExperimental evidence from in vitro models suggests that chronic hyperglycemia can induce extracellular matrix deposition in the trabecular meshwork, potentially obstructing aqueous humor outflow [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This extracellular matrix accumulation may include fibronectin and glycosaminoglycans, both of which are implicated in impaired aqueous drainage and elevated IOP [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGlycated hemoglobin (HbA1c) is a widely accepted biomarker for assessing long-term glycemic control [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Unlike prior studies that examined intraocular pressure primarily in diabetic cohorts, this study evaluates HbA1c as a continuous metabolic marker influencing intraocular pressure in both diabetic and non-diabetic individuals, thereby exploring glycemic control as an independent modifier of IOP.\u003c/p\u003e \u003c/div\u003e"},{"header":"Methods","content":"\u003cp\u003eThis prospective observational study was conducted at the University Clinical Center of Kosovo Eye Clinic and the Italian Eye Hospital in Prishtina, Kosovo between June 2022 and June 2024. The study was approved by the Ethical Commission of the University Clinical Center of Kosovo and the Faculty of Medicine at the University of Prishtina (Reference No. 4/291). Data on the association between HbA1c and intraocular pressure in Southeastern European diabetic and non-diabetic populations remain limited especially in a developing and new country such as Kosovo. All participants provided written informed consent prior to enrollment. The study adhered to the principles of the Declaration of Helsinki and complied with national regulations regarding the protection of personal data.\u003cbr\u003e\u0026nbsp;A total of 200 patients were screened, and 150 were included in the final analysis: 100 with a confirmed diagnosis of type 1 or type 2 diabetes and 50 non-diabetic controls. Diabetic participants included individuals with non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR). HbA1c was analyzed as a continuous biological variable of chronic hyperglycemia rather than dichotomized by diabetic status to better reflect metabolic exposure.\u003c/p\u003e\n\u003cp\u003eDemographic data, diabetes duration, smoking status, systemic comorbidities, and presence of diabetic retinopathy were recorded. HbA1c levels (measured within the preceding 3 months) were obtained from medical records; patients without recent results were instructed to obtain testing within 1 month, after which IOP was measured on the same day. IOP was measured using Goldmann applanation tonometry or non-contact pneumotonometry. Descriptive statistics were used to summarize demographic and clinical characteristics. Pearson correlation was used to evaluate the association between HbA1c and IOP. Between-group comparisons were performed using independent t tests. Linear regression analysis was used to model the relationship between HbA1c and IOP. A p value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethical Commission of the University Clinical Center of Kosovo and the Faculty of Medicine at the University of Prishtina (reference No. 4/291). All participants provided written informed consent prior to enrollment. The study adhered to the principles of the Declaration of Helsinki and complied with national regulations regarding the protection of personal data.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 150 participants were enrolled (49% male, 51% female), including 100 with diabetes and 50 non-diabetic controls. The mean age was 63.8 years for the diabetic group and 56.5 years for the control group. The mean duration of diabetes in the diabetic cohort was 16 years. Mean IOP was significantly higher in the diabetic group compared with controls for both the right eye (OD: 17.07 mmHg vs 14.26 mmHg, p \u0026lt; 0.001) and the left eye (OS: 16.89 mmHg vs 14.36 mmHg, p \u0026lt; 0.001). Mean HbA1c was also significantly higher among diabetic participants (6.99%) than controls (5.55%, p \u0026lt; 0.001). The prevalence of diabetic retinopathy (NPDR or PDR) among diabetic patients was 70%. Hypertension was present in 49% of diabetics and 32% of controls. Smoking was reported by 35% of diabetics and 34% of controls.\u003c/p\u003e\n\u003cp\u003eA scatter plot analysis demonstrated a positive association between HbA1c and IOP in both groups (Figure 1). Linear regression analysis confirmed statistical significance in both the control group (slope = 2.18, R² = 0.15, p = 0.0059) and the diabetic group (slope = 1.45, R² = 0.10, p = 0.0011). The coefficients of determination indicate that HbA1c accounts for a modest proportion of IOP variability.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrates that chronic glycemic exposure, reflected by HbA1c levels, is associated with intraocular pressure across individuals with and without diabetes, suggesting a metabolic influence on IOP that extends beyond traditional disease classifications. These findings suggest that hyperglycemia may play a role in ocular physiology beyond its established association with diabetic retinopathy and other diabetic ocular complications.\u0026nbsp;\u003cbr\u003e\u0026nbsp;Previous studies have reported a relationship between hyperglycemia and elevated IOP, although the underlying mechanisms remain incompletely understood [1-4]. Persistent hyperglycemia has been shown to induce histologic changes in the trabecular meshwork, including deposition of extracellular matrix components such as fibronectin and glycosaminoglycans, which may reduce aqueous humor outflow and contribute to IOP elevation [2-4]. Experimental work in animal models has demonstrated a two- to three-fold increase in aqueous humor glucose levels in diabetic compared with non-diabetic subjects, further supporting this mechanistic link [5-7]. These findings suggest that HbA1c may act as a metabolic modifier of intraocular pressure, potentially influencing clinical thresholds used for glaucoma risk assessment. Unlike prior studies that primarily compared diabetic and non-diabetic groups, the present study conceptualizes HbA1c as a continuous marker of metabolic exposure influencing intraocular pressure across the full glycemic and metabolic spectrum. The observed association within non-diabetic individuals suggests that even subclinical hyperglycemia may affect aqueous humor dynamics, supporting a metabolic rather than categorical disease model of IOP regulation\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;The present study aligns with epidemiologic evidence from large-scale cohorts, including the Framingham Eye Study and the Rotterdam Study, which have reported higher prevalence of ocular hypertension and glaucoma among individuals with diabetes [6-8]. \u0026nbsp;While the association in our study was statistically significant, the modest R² values suggest that HbA1c explains only part of the variability in IOP, indicating that additional factors—such as corneal thickness, ocular biomechanics, and systemic vascular health—also influence IOP regulation.\u003cbr\u003e\u0026nbsp;From a clinical perspective, these findings highlight the importance of integrating glycemic assessment into routine ophthalmologic evaluations, particularly for patients at risk of glaucoma. Screening for elevated IOP in individuals with poor glycemic control could enable earlier intervention and potentially reduce the risk of optic nerve damage.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurthermore, chronic glycemic exposure may influence intraocular pressure through multiple mechanisms, including increased trabecular meshwork extracellular matrix deposition, altered corneal biomechanics, and changes in aqueous humor osmolarity. These processes are not exclusive to overt diabetes and may begin at HbA1c levels traditionally considered non-pathologic.\u003c/p\u003e\n\u003cp\u003eFuture studies incorporating central corneal thickness, corneal hysteresis, and longitudinal glycemic monitoring would further clarify the metabolic contribution to IOP regulation.\u003c/p\u003e\n\n"},{"header":"Conclusion","content":"\u003cp\u003eThis study demonstrates a significant positive correlation between chronic hyperglycemia and intraocular pressure (IOP) in both diabetic and non-diabetic individuals. The consistent association across groups suggests that chronic hyperglycemia may contribute to IOP elevation, potentially increasing the risk of glaucomatous optic neuropathy. These findings support the integration of glycemic status assessment into routine ophthalmologic care, particularly for patients at elevated risk of glaucoma. Further longitudinal and mechanistic studies are warranted to determine whether improved glycemic control can reduce IOP and mitigate glaucoma risk.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eI would like to thank all my colleagues for providing administrative and material support. All authors have read and approved the manuscript. The manuscript and parts of it have not and will not be submitted elsewhere for publication. AI was used for checking of grammatical errors of the research paper.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial disclosure:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have nothing to disclose and no financial interests to disclose.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors declare that they have no conflicts of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e The data that support the findings in this study are available from the corresponding author upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKey Points:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e- \u003cstrong\u003eNovel finding\u003c/strong\u003e: \u003cstrong\u003eHbA1c acts as a continuous metabolic determinant of intraocular pressure independent of diabetes diagnosis.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e- Clinical implication: Elevated HbA1c may be a risk factor for increased IOP, independent of diabetes status.\u003c/p\u003e\n\u003cp\u003e- Relevance: Supports the integration of glycemic assessment into routine eye examinations for early detection of ocular hypertension and glaucoma.\u003c/p\u003e\n\u003cp\u003e- Research gap: Longitudinal studies are needed to clarify causality and evaluate the impact of glycemic control on IOP.\u003c/p\u003e\n\u003cp\u003e- Public health perspective: Early detection and management of hyperglycemia may help prevent glaucoma-related vision loss.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethical Commission of the University Clinical Center of Kosovo and the Faculty of Medicine at the University of Prishtina (reference No. 4/291). All participants provided written informed consent prior to enrollment. The study adhered to the principles of the Declaration of Helsinki and complied with national regulations regarding the protection of personal data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Consent:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors want to specify that they have obtained a written signed patient consent for the use of their information and the data. All patients included in this study have given their informed consent in order for their clinical information and images to be used and reported in this publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of Contribution:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr.Agon Rrusta conceived and designed the study and collected the data.\u003c/p\u003e\n\u003cp\u003eDr.Agon Rrusta, Prof.asoc.Gazmend Kacaniku, Dr.Ferdije Brahimi, Dr.Shpat Rrusta, Dr.Dile Rrusta collected the data.\u003c/p\u003e\n\u003cp\u003eDr.Agon Rrusta and Prof.Gazmend Kacaniku performed the statistical analysis and drafted the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eProf.asoc. Gazmend Kacaniku and Prof.asoc Ali Tonuzi revised the manuscript.\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final version of the manuscript.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHymowitz MB, Chang D, Feinberg EB, Roy S. Increased intraocular pressure and hyperglycemic level in diabetic patients. PLoS One. 2016;11(3):e0151833. doi:10.1371/journal.pone.0151833.\u003c/li\u003e\n\u003cli\u003eMatsuoka M, Ogata N, Matsuyama K, Yoshikawa T, Takahashi K. Intraocular pressure in Japanese diabetic patients. Clin Ophthalmol. 2012;6:1005-1009. doi:10.2147/OPTH.S33131.\u003c/li\u003e\n\u003cli\u003eKing H, Aubert RE, Herman WH. Global burden of diabetes, 1995\u0026ndash;2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998;21(9):1414-1431. doi:10.2337/diacare.21.9.1414.\u003c/li\u003e\n\u003cli\u003eBacharach J, Delgado MF, Iwach AG. Comparison of the efficacy of the fixed-combination timolol/dorzolamide versus concomitant administration of timolol and dorzolamide. J Ocul Pharmacol Ther. 2003;19(2):93-96. doi:10.1089/108076803321636440.\u003c/li\u003e\n\u003cli\u003eKlein BE, Klein R, Jensen SC. Open-angle glaucoma and older-onset diabetes: The Beaver Dam Eye Study. Ophthalmology. 1994;101(1):117-121. doi:10.1016/S0161-6420(94)31355-7.\u003c/li\u003e\n\u003cli\u003eOshitari T, Roy S. Effect of chronic hyperglycemia on intraocular pressure in patients with diabetes. Am J Ophthalmol. 2007;143(2):363-365. doi:10.1016/j.ajo.2006.09.030.\u003c/li\u003e\n\u003cli\u003eKahn HA, Milton RC. Revised Framingham Eye Study: prevalence of glaucoma and diabetic retinopathy. Am J Epidemiol. 1980;111(6):769-776. doi:10.1093/oxfordjournals.aje.a112954.\u003c/li\u003e\n\u003cli\u003eSato T, Roy S. Effect of high glucose on fibronectin expression and cell proliferation in trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2002;43(1):170-175.\u003c/li\u003e\n\u003cli\u003eRohen JW. Why is intraocular pressure elevated in chronic simple glaucoma? Anatomic considerations. Ophthalmology. 1983;90(7):758-765. doi:10.1016/S0161-6420(83)34520-2.\u003c/li\u003e\n\u003cli\u003eBabizhayev MA, Brodskaya MW. Fibronectin detection in drainage outflow system of human eyes in ageing and progression of open-angle glaucoma. Mech Ageing Dev. 1989;47(2):145-157. doi:10.1016/0047-6374(89)90021-8.\u003c/li\u003e\n\u003cli\u003ePerez-Rico C, Gutierrez-Ortiz C, Gonzalez-Mesa A, et al. Effect of diabetes mellitus on Corvis ST measurement process. Acta Ophthalmol. 2015;93(3):e193-e198. doi:10.1111/aos.12530.\u003c/li\u003e\n\u003cli\u003eRombold F, Thiel MJ, Neubauer AS, Hirneiss C, Kampik A. Evaluation of portable TGDc-01 tonometers and comparison with the Goldmann applanation tonometer. Ophthalmologe. 2005;102(2):158-162. doi:10.1007/s00347-004-1078-1.\u003c/li\u003e\n\u003cli\u003eDielemans I, de Jong PT, Stolk R, Vingerling JR, Grobbee DE, Hofman A. Primary open-angle glaucoma, intraocular pressure, and diabetes mellitus in the general elderly population: The Rotterdam Study. Ophthalmology. 1996;103(8):1271-1275. doi:10.1016/S0161-6420(96)30505-7.\u003c/li\u003e\n\u003cli\u003eL\u0026uuml;tjen-Drecoll E. Functional morphology of the trabecular meshwork in primate eyes. Prog Retin Eye Res. 1999;18(1):91-119. doi:10.1016/S1350-9462(98)00011-1.\u003c/li\u003e\n\u003cli\u003eBraha A, Simion A, Timar R, Timar B. Factors Associated with Increased Intraocular Pressure in Type 2 Diabetes Patients. \u003cem\u003eJournal of Clinical Medicine\u003c/em\u003e. 2024; 13(3):676. https://doi.org/10.3390/jcm13030676.\u003c/li\u003e\n\u003cli\u003eSamal, A., Panda, L., Khan, Z. U., Dash, R. J., \u0026amp; Sahoo, K. K. (2021). Study of intraocular pressure in diabetes mellitus patients. \u003cem\u003eInternational Journal of Science and Healthcare Research\u003c/em\u003e, \u003cem\u003e6\u003c/em\u003e(1), 21-29.\u003c/li\u003e\n\u003cli\u003ePimentel LG, Gracitelli CP, da Silva LS, Souza AK, Prata TS. Association between Glucose Levels and Intraocular Pressure: Pre- and Postprandial Analysis in Diabetic and Nondiabetic Patients. J Ophthalmol. 2015;2015:832058. doi: 10.1155/2015/832058. Epub 2015 Jan 6. PMID: 25642344; PMCID: PMC4302384.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Demographic and Clinical Characteristics of Study Participants\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAll Participants (n=150)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDiabetes (n=100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eControl (n=50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge, mean (y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e63.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e56.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale sex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e40 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFemale sex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e60 (60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDuration of diabetes, mean (y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIOP, mean (mmHg) OD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIOP, mean (mmHg) OS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHbA1c, mean (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDiabetic retinopathy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e70 (70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHypertension, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e49 (49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSmoking, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e35 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17 (34)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOther systemic disorders, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e41 (41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eType 1 diabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eType 2 diabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e80 (80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Linear Regression Results for the Relationship Between HbA1c and IOP\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSlope\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIntercept\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003er Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eR²\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ep Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStandard Error\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.388\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.0059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.757\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDiabetic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.320\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.0011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.431\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"University of Prishtina","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":"Diabetus Mellitus, hyperglycemia, intraocular pressure, glaucoma, diabetic retinopathy","lastPublishedDoi":"10.21203/rs.3.rs-8575724/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8575724/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eElevated intraocular pressure (IOP) has been associated with diabetes mellitus; however, the role of chronic hyperglycemia in both diabetic and non-diabetic patients remain a topic of exploration with regard to dysregulation of trabecular meshwork and humor aqueous drainage especially in understudied regions such as Kosovo and Southeast Europe.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo evaluate glycated hemoglobin (HbA1c) as a continuous metabolic determinant of intraocular pressure independent of diabetes mellitus diagnosis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this prospective observational study, 150 participants (100 with diabetes and 50 non-diabetic controls) were enrolled. HbA1c values obtained within three months of ocular examination were analyzed as a continuous variable. IOP was measured using applanation or non-contact tonometry. Associations between HbA1c and IOP were assessed using correlation and linear regression analyses.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eMean IOP was significantly higher in diabetic participants compared with controls (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Across the entire cohort, HbA1c demonstrated a significant positive association with IOP, including within the non-diabetic range. Linear regression confirmed HbA1c as an independent predictor of IOP in both diabetic (R\u0026sup2; = 0.10, p\u0026thinsp;=\u0026thinsp;0.0011) and non-diabetic individuals (R\u0026sup2; = 0.15, p\u0026thinsp;=\u0026thinsp;0.0059).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eChronic hyperglycemia is associated with intraocular pressure across diabetic and non-diabetic populations, suggesting that chronic glycemic exposure may influence ocular physiology beyond conventional disease classifications. These findings support the consideration of metabolic glycemic status in glaucoma risk assessment in this population.\u003c/p\u003e","manuscriptTitle":"Glycated hemoglobin as a continuous metabolic determinant of intraocular pressure independent of diabetic status: a prospective observational study in Kosovo","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-16 08:53:03","doi":"10.21203/rs.3.rs-8575724/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":"725e3d9e-e639-40a8-b523-5d15901e553d","owner":[],"postedDate":"January 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":60950639,"name":"Ophthalmology"}],"tags":[],"updatedAt":"2026-01-16T08:53:03+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-16 08:53:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8575724","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8575724","identity":"rs-8575724","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}