Characteristics of the Meibomian gland in a population without dry eye symptoms

Characteristics of the Meibomian gland in a population without dry eye symptoms | 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 Article Characteristics of the Meibomian gland in a population without dry eye symptoms Sathiya Kengpunpanich, Pinnita Prabhasawat, Rawi Jongpipatchai, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6869046/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted 17 You are reading this latest preprint version Abstract This prospective cross-sectional study examined morphological and functional changes of the meibomian glands in 60 healthy volunteers without dry eye symptoms, stratified into age groups of 31- 40, 41-50, and 51-60 years. Participants were screened using the DEQS questionnaire (score≤14) and underwent ocular assessments, including slit lamp examination, fluorescein tear breakup time (FTBUT), Schirmer test, lipid layer thickness (LLT), blink quality, meibography, evaluation of meibomian gland expressibility, and meibum quality. The results showed an abnormal morphology of the meibomian gland (Meiboscore ≥1) in 71% of the upper lids and 51% of the lower lids, with significant age-related differences. Lid margin abnormalities, such as telangiectasia (82%) and gland plugging (84%), were common in the normal population, while lid margin irregularity (11%) varied significantly by age. Tear function tests revealed a median Schirmer I score of 10 mm. (P=0.01 between age groups) and FTBUT of 5.04 seconds. LLT averaged 61 ± 20 microns and corneal staining abnormalities, graded using the Oxford scale, were observed in 23.3% (grade 1) and 1.7% (grade 2). Expressibility and meibum quality abnormalities were found in 66% and 65% of the participants, respectively. The study highlights significant age-related degenerative changes in the meibomian gland morphology of individuals without dry eye symptoms. Although the tear film remains preserved, these findings suggest that awareness, along with early detection and treatment of MGD, might be necessary to prevent the onset of symptoms and the development of dry eye disease. Health sciences/Health care/Disease prevention Health sciences/Medical research/Study design Health sciences/Signs and symptoms/Eye manifestations Meibomian gland dysfunction Meibomian gland characteristic change non-dry eye population Figures Figure 1 Introduction The Meibomian glands play a crucial role in maintaining the health and stability of the tear film on the ocular surface by producing a lipid layer that prevents excessive tear evaporation 1 . Dysfunction of these glands can manifest itself in various ocular problems, including dry eye disease, blepharitis, intolerance to contact lens wear, and conjunctivitis, emphasizing their critical role in preserving ocular surface health and comfort 2 – 7 . Moreover, Meibomian gland dysfunction (MGD) is widely recognized as the primary factor contributing to evaporative dry eye 2 . Various assessment tools are used to evaluate both signs and symptoms of MGD. The recommended diagnostic tests for MGD and MGD-associated conditions included symptom-related questionnaires, lid morphology evaluation 8 , gland expressibility assessment 9 , tear film lipid layer analysis, tears osmolarity measurement, fluorescein tear breakup time (FTBUT), ocular surface staining, and Schirmer 1 test for tear secretion. Changes in the meibomian glands are often associated with dry eye disease. Few studies have examined the meibomian glands in individuals with no obvious eyelid or ocular surface disorders. For example, the study by Arita et al. 10 demonstrated changes in the meibomian glands, as detected by non-contact meibography, increased with age and appeared earlier in males than in females. Moreover, another study by Srivastav, et al. 11 revealed that morphological abnormalities of the meibomian glands, such as distortion, tortuosity, hooking, overlapping, abnormal gaps, dropout, and shortened glands, can also be observed in healthy individuals. However, no studies have examined whether alterations in the meibomian glands, eyelid characteristics, and ocular surface condition occur in individuals who do not have dry eye disease. Therefore, it is interesting to investigate the morphological and functional changes of meibomian glands in asymptomatic individuals and to determine the extent of meibomian gland changes in those without dry eye disease. Understanding these early gland changes in non-dry eye patients is crucial, as they could represent a preliminary stage in the progression toward dry eye disease. By recognizing and potentially managing these meibomian gland alterations early, there may be an opportunity to preserve long-term eye health, maintain optimal tear film stability, and prevent future dry eye symptoms. This evolving perspective on meibomian gland changes in non-dry eye individuals opens the door to new approaches in proactive ocular care and sheds light on the complexity of tear film and eyelid health. Methods Study Design This was a cross-sectional study aimed at examining the morphological and functional changes in meibomian glands among 60 non-dry-eye individuals. The study adhered to the principles of the Declaration of Helsinki and received approval from the Committee for the Protection of Human Participants in Research at the Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand (COA no. Si 367/2022). Informed consent was obtained from all subjects prior to enrollment. Participants This study recruited 60 healthy volunteers, aged between 31 and 60 years. Participants were stratified into three age groups (31–40, 41–50, 51–60), with each group consisting of 20 individuals. The focus of our study centered on subjects without dry eye symptoms, identified through Dry Eye-Related Quality of Life scores (DEQS) registering at 14 or lower 12 . To ensure the exclusion of other factors that could potentially influence meibomian gland function and dry eye symptoms, exclusion criteria include individuals with eye conditions e.g., dry eye, infections, recent eye surgery, previous refractive surgery, systemic diseases affecting the eyes, regular eye drop or artificial tears use, contact lens wear, recent experimental drug use, recent treatments for MGD, and recent use of certain anti-inflammatory medications. Study Procedures The examination proceeded sequentially, starting with the measurement of lipid layer thickness (LLT) using LipiView™ II Ocular Surface Interferometer, followed by slit-lamp observation of lid margin abnormalities and corneal surface staining using the Modified Oxford Scale. Subsequently, three consecutive measurements of FTBUT were conducted. Tear film production was evaluated using the Schirmer test without a topical anesthetic. The meibomian glands in the upper and lower eyelids were observed using noncontact meibography via the LipiView™ II Ocular Surface Interferometer and then converted to meiboscore. The meiboscore grades the extent of meibomian gland loss as follows: 0 indicates no loss; 1 represents loss of less than one-third of the eyelid length; 2 denotes loss between one-third and less than two-thirds; and 3 signifies loss exceeding two-thirds of the eyelid length 10 . Lastly, a meibomian gland expressibility and meibum quality assessment was performed by pressing the eyelids with a meibomian gland evaluator. All examinations were completed the same day by a single investigator. Detailed descriptions of the outcome measurements are provided in the Supplement . Statistical Analysis Data were collected from both eyes and statistical analysis was conducted using SPSS version 29 (IBM). Descriptive statistics were reported as mean ± standard deviation (SD) for normally distributed data and median (IQR) for skewed data. Generalized Estimating Equations (GEE) were employed to compare outcomes among three age groups while adjusting for the correlation between the two eyes. All statistical tests were two-tailed. Results Among the 60 volunteers, 38 were females. All volunteers had no dry eye symptoms, with a DEQS score of 14 or lower. Demographic data including age, sex, and DEQS score in this study were stratified into age groups (31–40, 41–50, 51–60), with an equal distribution of 20 subjects in each age group, as shown in Table 1 . Alterations in Meibomian gland morphology, or meibomian gland loss, quantified by meiboscore 10 , were observed in both eyelids, with severity increasing with age, as demonstrated in Fig. 1 , exhibited abnormalities (Meiboscore ≥ 1) in 71% of the upper lid and 51% of the lower lid when combining all age groups, with statistically significant differences observed between the three distinct ages (P < 0.001 and P = 0.04, respectively). Abnormal Meibomian glands (Meiboscore ≥ 1) in the upper eyelids were found in 62.5%, 70%, and 80% of individuals aged 31–40, 41–50, and 51–60 years, respectively. Similarly, lower eyelid abnormalities were observed in 37.5%, 47.5%, and 67.5% of individuals in the same age groups, respectively. Most subjects exhibited abnormal meibomian gland morphology in both the upper and lower eyelids. Lid margin abnormalities were identified (Grade1-3 in supplement) in all age groups of healthy volunteers, including characteristics such as margin telangiectasia, meibomian gland plugging, and lid irregularity with frequencies of 82%, 84%, and 12%, respectively. These findings demonstrated that such abnormalities can occur even in individuals without dry eye symptoms. Notably, among lid margin abnormalities, only lid irregularity demonstrated a statistically significant difference among the various age groups (P = 0.01) as shown in Table 2 . Regarding tear function evaluation, the median Schirmer I test was recorded at 10 mm (P25 = 3.2, P75 = 29.7), while the median FTBUT was 5.04 seconds (P25 = 3.71, P75 = 7.61). In particular, the Schirmer I test revealed a significant difference between the age groups (P = 0.015). For the thickness of the lipid layer, there were several parameters, including average, minimal and maximal LLT, as shown in the Table 2 . The average LLT for all age groups was 61 ± 20 µm. In the 51–60 age group, the average minimal LLT measured 44 µm, showing a significant decrease compared to the 41–50 age group, where the average was 54 µm (P = 0.03). Analysis of corneal staining using the Oxford scheme indicated abnormalities with 23.3% and 1.7% presenting at grade 1 and grade 2, respectively. Furthermore, assessments of expressibility and meibum quality demonstrated abnormalities in 66% and 65% of cases, respectively, within the study cohort, as shown in Table 2 . Discussion In this study, notable anatomical and functional changes in the meibomian glands were observed among non-dry eye populations aged 30-60 years. Additionally, abnormalities of the lid margin, such as telangiectasia, meibomian gland plugging, and irregularities, were also demonstrated. As in the results, more than half of the subjects had anatomical lid abnormalities and meibomian gland loss in both the upper and lower eyelids. Meibomian gland loss, lid irregularity, Schirmer I test, and minimum LLT were found to change significantly with age. Although individuals do not report symptoms of dry eyes, there is evidence of meibomian gland and eyelid abnormalities, which tend to show an increasing trend with advancing age. Our results were compatible with a previous study by Arita et al 10 , which provided a large-scale analysis of meibomian gland changes, focusing on abnormalities in the general population. Meibomian gland dropout was observed in 55% of eyes across an age range of 21 to 93 years, showing a significant association with aging in both males and females. The present study demonstrated a significant increase in meibomian gland loss with age, with abnormal meibomian glands (Meiboscore ≥1) observed more frequently in the upper eyelids (71%) than in the lower eyelids (51%). Some imaging studies have revealed similar results to ours as they found a higher prevalence of meibomian gland dropout in the upper eyelids 11,13 , while others have reported more gland alterations in the lower eyelids 14 . This inconsistency is speculated to result from variations in anatomical, functional, and mechanical factors of each individual. The current study specifically focused on individuals (age ranged between 30-60 years) who did not have any dry eye symptoms. A notable number of characteristic meibomian gland changes were still found in these subjects. As we kwow, the tear film lipid layer, primarily derived from the meibomian glands, is essential for tear stability, reducing evaporation, and protecting the ocular surface 15 . LLT was found to be positively correlated with tear breakup time 16-18 . Previous studies have reported normal LLT values ranging from 42 to 88 nm 19-22 , with most healthy individuals exhibiting LLT around 60-80 nm. 23 This values can vary depending on measurement methods, age, ethnicity, and environmental factors 24 . In our study, the mean LLT range was 57-63 nm, which may explain why all subjects reported no dry eye symptoms. Interestingly, the participants in this study could maintain normal LLT, tear break-up time (TBUT), and Schirmer test results despite more than 50% of subjects exhibiting meibomian gland loss and reduced meibum expressibility. The compensatory capacity of the remaining meibomain glands might allow them to maintain secretory function to a certain threshold, beyond which their function becomes evident, manifesting as a short FTBUT, dry eye symptoms, and ocular surface staining. However, LLT showed a declining trend with age, corresponding to the progression of meibomian gland loss, particularly evident in the 51-60 year old group across all parameters. These findings suggested that MGD may develop subclinically before symptoms becomes apparent. The loss of meibomian glands in both the upper and lower eyelids is associated with thinner lipid layers 25,26 . As mentioned earlier, we found lower meiboscores in the lower eyelids of a non-dry eye population, aligning with previous research suggesting that MGD tends to be less severe in the lower lids compared to the upper lids 27 . This may have a unique relationship with dry eye symptoms 25,26 , possibly explaining the absence of symptoms in these individuals, contrasting with symptomatic populations where lower lid meibomian gland loss is more pronounced. These findings underscore the importance of regional differences in meibomian gland loss and their potential role in the development of dry eye symptoms. Further research is warranted to clarify these relationships and their clinical implications. Regarding lid irregularity, it was found to be less prevalent, with only 10% of subjects exhibiting this feature, suggesting relatively intact lid morphology in the study population. In a study conducted by M. Ha et al 25 , the correlation between lid margin irregularities and meibomian gland loss was examined using infrared-meibography in patients diagnosed with dry eye disease. They found that only irregularities in the lid margin were associated with meibomian gland dropout. In comparison, our study, which focused on a non-dry eye population, also observed much lower prevalence of lid margin irregularities. Therefore, lid margin irregularity may be considered a significant marker for determining MGD severity in symptomatic patients, rather than in the general population. To the best of our knowledge, this is the first study to analyze meibomian gland characteristics specifucally focus on a non-dry eye population. The findings reveal distinct morphological changes in the meibomian glands, even among individuals without dry eye symptoms. Despite these gland abnormalities, lipid tear film function appeared to be preserved, as reflected by normal LLT values. This observation emphasizes the nature of ocular surface health and underscores the possibility of a dissociation between MG features and other components of tear film dynamics in individuals without overt dry eye symptoms. This study has some limitations. First, the non-dry eye population examined in this study may not fully represent the diversity of the broad population, as the sample size was relatively modest and limited to a single ethnic group, thereby restricting the generalizability of the findings to other ethnicities. In addition, participant age was confined to 30–60 years. Individuals within this age group may share similar behaviors, activities, and lifestyle factors, which may not accurately reflect the characteristics of younger or older populations. Lastly, as a cross-sectional study, the findings capture only a single time point, leaving the long-term progression and outcomes of meibomian gland changes unexamined. These aspects highlight opportunities for future research, particularly longitudinal studies, to better elucidate the progression and significance of the observed findings. In conclusion, this study identified notable meibomian gland abnormalities in individuals without dry eye symptoms, correlating with age. This draws attention to consider age-related variations in interpreting the health of the meibomian glands. Moreover, the findings suggest that the meibomian gland changes can occur even in the absence of dry eye symptoms, highlighting the potential need for early awareness and consideration of preventing interventions to halt disease progression. Further cohort studies are required to better understand these findings and to explore effective strategies for managing and slowing the progression of meibomian gland changes. Declarations Conflict of interest: No conflicting relationship exists for any author. Funding This study was funded by the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, Grant number: R016231048. Author Contribution Kengpunpanich S. interpreted and analysed of data, wrote the main manuscript text and approved the submitted versionPrabhasawat P. created and designed of the research work, and interpreted of dataJongpipatchai R. prepared figures 1 and Table1,2, collected and analysed the dataChirapapaisan C. designed of the research work , wrote the main manuscrip and approved the submitted versionNgowyutagon P. and Booranapong W. approved the submitted versionAll authors reviewed the manuscript. Data Availability The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. References Tomlinson, A. et al. The international workshop on meibomian gland dysfunction: report of the diagnosis subcommittee. Invest Ophthalmol Vis Sci,52, 2006–2049 (2011). Nichols, K. K. et al. The International Workshop on Meibomian Gland Dysfunction: Executive Summary. Invest Ophthalmol Vis Sci, 52, 1922–1929 (2011). Asiedu, K. et al. Meibomian Gland Dysfunction in a Youthful Clinical Sample in Ghana. Optom. Vis. Sci. 95 , 349–353 (2018). Mathers, W. D. et al. Meibomian gland dysfunction in chronic blepharitis. Cornea 10 , 277–285 (1991). Lemp, M. A. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. CLAO J. 21 , 221–232 (1995). Mathers, W. D. Ocular evaporation in meibomian gland dysfunction and dry eye. Ophthalmology 100 , 347–351 (1993). Shimazaki, J. et al. Ocular surface changes and discomfort in patients with meibomian gland dysfunction. Arch. Ophthalmol. 113 , 1266–1270 (1995). Bron, A. J. et al. Meibomian gland disease. Classification and grading of lid changes. Eye (London England) . 5 (Pt 4), 395–411 (1991). Foulks, G. N. & Bron, A. J. Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification, and grading. Ocul Surf. 1 , 107–126 (2003). Arita, R. et al. Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population. Ophthalmology 115 , 911–915 (2008). Srivastav, S. et al. Morphologic variants of Meibomian glands: age wise distribution and differences between upper and lower eyelids. Front. Med. (Lausanne) . 10 , 1195568 (2023). Sakane, Y. et al. Development and Validation of the Dry Eye–Related Quality-of-Life Score Questionnaire. JAMA Ophthalmol. 131 , 1331–1338 (2013). Chen, X. et al. Morphology of Meibomian Glands in a 65-Year-Old Norwegian Population without Dry Eye Disease. J. Clin. Med. ; 11 (3). (2022). Alsuhaibani, A. H., Carter, K. D., Abràmoff, M. D. & Nerad, J. A. Utility of meibography in the evaluation of meibomian glands morphology in normal and diseased eyelids. Saudi J. ophthalmology: official J. Saudi Ophthalmological Soc. 25 (1), 61–66 (2011). Cwiklik, L. Tear film lipid layer: A molecular level view. Biochim. Biophys. Acta . 1858 , 2421–2430 (2016). Isreb, M. A. et al. Correlation of lipid layer thickness measurements with fluorescein tear film break-up time and Schirmer's test. Eye (Lond) . 17 , 79–83 (2003). Li, Y. et al. Relationship between lipid layer thickness, incomplete blinking rate and tear film instability in patients with different myopia degrees after small-incision lenticule extraction. PloS one . 15 , e0230119 (2020). Ji, Y. W. et al. Automated Measurement of Tear Film Dynamics and Lipid Layer Thickness for Assessment of Non-Sjögren Dry Eye Syndrome With Meibomian Gland Dysfunction. Cornea 36 , 176–182 (2017). King-Smith, P. E. et al. Application of a novel interferometric method to investigate the relation between lipid layer thickness and tear film thinning. Invest. Ophthalmol. Vis. Sci. 51 , 2418–2423 (2010). McDonald, J. E. Surface phenomena of tear films. Trans. Am. Ophthalmol. Soc. 66 , 905–939 (1968). Kim, W. J. et al. Lipid layer thickness decrease due to meibomian gland dysfunction leads to tear film instability and reflex tear secretion. Ann. Med. 54 , 893–899 (2022). Lee, Y. et al. Characteristics of dry eye patients with thick tear film lipid layers evaluated by a LipiView II interferometer. Graefes Arch. Clin. Exp. Ophthalmol. 259 , 1235–1241 (2021). Bron, A. J. & Tiffany, J. M. The contribution of meibomian disease to dry eye. Ocul Surf . ;2(2):149 – 65. (2004). 10.1016/S1542-0124(12)70046-6 . PMID: 16985755. Jung, J. W. et al. Analysis of Factors Associated With the Tear Film Lipid Layer Thickness in Normal Eyes and Patients With Dry Eye Syndrome. Invest. Ophthalmol. Vis. Sci. 57 , 4076–4083 (2016). Korb, D. R. & Blackie, C. A. Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and gland location. Cornea 27 , 1142–1147 (2008). Ha, M. et al. Relationship between eyelid margin irregularity and meibomian gland dropout. Ocul Surf. 19 , 31–37 (2021). Golebiowski, B. et al. Lid margins: sensitivity, staining, meibomian gland dysfunction, and symptoms. Optom. Vis. Sci. 89 , 1443–1449 (2012). Tables Table 1. Demonstrated the demographic characteristics of the study participants. Demographic data Total Age group: Number (%) 31-40 (n=20) 41-50 (n=20) 51-60 (n=20) Age, years, (mean) 44.6 36 43 55 Female, n (%) 38 (63.3) 13 (65.0) 12 (60.0) 13 (65.0) DEQS (mean) 4.5 5 5 4 n: number of participants Table 2. Summary of the outcome parameters in patients without dry eyes between age groups. Outcome measures Total Age group P-value 31-40 (n=40) 41-50 (n=40) 51-60 (n=40) Lid characteristics Lid telangiectasia Grade 0, n (%) 22 (18.3%) 6 (15.0%) 10 (25.0%) 6 (15.0%) 0.54 Grade 1, n (%) 39 (32.5%) 18 (45.0%) 12 (30.0%) 9 (22.5%) Grade 2, n (%) 53 (44.2%) 12 (30.0%) 18 (45.0%) 23 (57.5%) Grade 3, n (%) 6 (5.0%) 4 (10.0%) 0 2 (5%) Meibomian gland plug Grade 0, n (%) 19 (15.8%) 9 (22.5%) 5 (12.5%) 5 (12.5%) 0.22 Grade 1, n (%) 64 (53.3%) 24 (60.0%) 19 (47.5%) 21 (52.5%) Grade 2, n (%) 36 (30.0%) 7 (17.5%) 16 (40.0%) 13 (32.5%) Grade 3, n (%) 1 (0.8%) 0 0 1 (2.5%) Lid irregularity Grade 0, n (%) 106 (88.2%) 37 (92.5%) 39 (97.5%) 30 (75.0%) 0.01* Grade 1, n (%) 14 (11.8%) 3 (7.5%) 1 (2.5%) 10 (25.0%) Grade 2, n (%) 0 0 0 0 Grade 3, n (%) 0 0 0 0 Meibomian expressibility Grade 0, n (%) 41 (34.2%) 14 (35.0%) 14 (35.0%) 13 (32.5%) 0.89 Grade 1, n (%) 39 (32.5%) 12 (30.0%) 12 (30.0%) 15 (37.5%) Grade 2, n (%) 36 (30.0%) 12 (30.0%) 12 (30.0%) 12 (30.0%) Grade 3, n (%) 4 (3.3%) 2 (5.0%) 2 (5.0%) 0 Meibum quality Grade 0, n (%) 42 (35.0%) 17 (42.5%) 16 (40.0%) 9 (22.5%) 0.09 Grade 1, n (%) 59 (49.2%) 17 (42.5%) 19 (47.5%) 23 (57.5%) Grade 2, n (%) 14 (11.7%) 4 (10.0%) 2 (5.0%) 8 (20.0%) Grade 3, n (%) 5 (4.2%) 2 (5.0%) 3 (7.5%) 0 Schirmer I: [Median (IQR), mm] 10 (3.2-29.7) 25.5 (3.2-35.0) 12.5 (4.0-28.5) 7.0 (3.0-14.0) 0.015* Lipid layer thickness (LLT) Average LTT [mean ±SD, µm] 61 ± 20 63 ± 22 62 ± 17 57 ± 19 0.28 Minimum LLT [mean ±SD, µm] 50 ± 21 54 ± 25 54 ± 18 44 ± 18 0.03* Maximum LLT [Med (IQR), µm] 81 (68-99) 83.5 (68.2-100.0) 82.5 (75.0-97.0) 78.0 (62.5-93.7) 0.54 FTBUT: [Median (IQR), sec] 5.04 (3.71-7.61) 5.32 (3.90-6.85) 4.52 (3.46-10.94) 5.12 (4.12-6.95) 1 Ocular surface staining* Grade 0, n (%) 90 (75) 30 (75.0) 31 (77.5) 29 (72.5) 0.52 Grade 1, n (%) 28 (23.3) 8 (20.0) 9 (22.5) 11 (27.5) Grade 2, n (%) 2 (1.7) 2 (5.0) 0 0 *Modified Oxford scale n: number of eyes Additional Declarations No competing interests reported. Supplementary Files Supplement.docx Cite Share Download PDF Status: Published Journal Publication published 16 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 26 Aug, 2025 Reviews received at journal 18 Aug, 2025 Reviews received at journal 17 Aug, 2025 Reviews received at journal 16 Aug, 2025 Reviewers agreed at journal 13 Aug, 2025 Reviewers agreed at journal 11 Aug, 2025 Reviewers agreed at journal 10 Aug, 2025 Reviewers agreed at journal 10 Aug, 2025 Reviewers agreed at journal 10 Aug, 2025 Reviews received at journal 02 Aug, 2025 Reviewers agreed at journal 18 Jul, 2025 Reviewers agreed at journal 13 Jul, 2025 Reviewers invited by journal 13 Jul, 2025 Editor assigned by journal 13 Jul, 2025 Editor invited by journal 17 Jun, 2025 Submission checks completed at journal 13 Jun, 2025 First submitted to journal 13 Jun, 2025 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. 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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-6869046","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":486206367,"identity":"545adacb-55b5-48e4-b6fa-af6dd16783fb","order_by":0,"name":"Sathiya Kengpunpanich","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Sathiya","middleName":"","lastName":"Kengpunpanich","suffix":""},{"id":486206368,"identity":"c89544d5-3bc8-4895-8265-8cdd87a6230f","order_by":1,"name":"Pinnita Prabhasawat","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Pinnita","middleName":"","lastName":"Prabhasawat","suffix":""},{"id":486206370,"identity":"7c6ff45d-02ee-425d-9d16-c54a02b5cb5c","order_by":2,"name":"Rawi Jongpipatchai","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Rawi","middleName":"","lastName":"Jongpipatchai","suffix":""},{"id":486206376,"identity":"503ef15f-b4e7-4438-a9f8-7ecd426e43b8","order_by":3,"name":"Chareenun Chirapapaisan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCUlEQVRIiWNgGAWjYDACCQSTjSGhgoHBgJnBgOEBWICHGC1noFoSwHxitDC2AbUwENDCP7v52YcPFXcStzMwP3vwcN42eXN25o0PEhjs5Bnkew9gteTOMeOZM848S9zZwGZukLjttuHOZrZigwSGZMMGNr4EbFoMJBKMmXnbDiduOMDDJgHUwrjhMI+ZRAIDcwLQYQbYtaR/Zv77D6Zlzm17qJZ6PFpyjJkZG2BaGm4nQrUcxqlF4kZOMWPPscPGGw6zAVUeu50MZAD9YnDcsI0tB6sW/hnpmxl+1ByW3XC8+Znkj5rbthvOH9744ENFtTw/8xmsWhCAGdXBoGgaBaNgFIyCUUAuAAC3LV1u86/B1QAAAABJRU5ErkJggg==","orcid":"","institution":"Mahidol University","correspondingAuthor":true,"prefix":"","firstName":"Chareenun","middleName":"","lastName":"Chirapapaisan","suffix":""},{"id":486206377,"identity":"8f8bf097-b686-4480-9a71-0c004b891554","order_by":4,"name":"Panotsom Ngowyutagon","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Panotsom","middleName":"","lastName":"Ngowyutagon","suffix":""},{"id":486206380,"identity":"3716cab7-04e1-4583-a7e2-75b18919762c","order_by":5,"name":"Wipawee Booranapong","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Wipawee","middleName":"","lastName":"Booranapong","suffix":""}],"badges":[],"createdAt":"2025-06-11 07:38:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6869046/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6869046/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-27641-2","type":"published","date":"2025-12-16T15:57:17+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":87032629,"identity":"08151829-1140-49f7-a121-6ae7f875b7c1","added_by":"auto","created_at":"2025-07-18 13:00:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":25725,"visible":true,"origin":"","legend":"\u003cp\u003eIllustrated a bar chart representing the distribution of Meiboscore across different age groups. (A) Meiboscore for the upper eyelid and (B) Meiboscore for the lower eyelid\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-6869046/v1/efdbb68c912eeebe7977509d.png"},{"id":98814831,"identity":"b30d8820-fbd6-478e-bd6c-4151fd70aad1","added_by":"auto","created_at":"2025-12-22 16:12:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":779550,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6869046/v1/45d17ac4-e89e-422c-8079-9c88d597ab51.pdf"},{"id":87032631,"identity":"688b0688-350a-4e4f-9d3e-8685958ff2a7","added_by":"auto","created_at":"2025-07-18 13:00:48","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":15837,"visible":true,"origin":"","legend":"","description":"","filename":"Supplement.docx","url":"https://assets-eu.researchsquare.com/files/rs-6869046/v1/6f94aa4394b880e9c2b872f0.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Characteristics of the Meibomian gland in a population without dry eye symptoms","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe Meibomian glands play a crucial role in maintaining the health and stability of the tear film on the ocular surface by producing a lipid layer that prevents excessive tear evaporation\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Dysfunction of these glands can manifest itself in various ocular problems, including dry eye disease, blepharitis, intolerance to contact lens wear, and conjunctivitis, emphasizing their critical role in preserving ocular surface health and comfort\u003csup\u003e\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Moreover, Meibomian gland dysfunction (MGD) is widely recognized as the primary factor contributing to evaporative dry eye\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Various assessment tools are used to evaluate both signs and symptoms of MGD. The recommended diagnostic tests for MGD and MGD-associated conditions included symptom-related questionnaires, lid morphology evaluation\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e, gland expressibility assessment\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e, tear film lipid layer analysis, tears osmolarity measurement, fluorescein tear breakup time (FTBUT), ocular surface staining, and Schirmer 1 test for tear secretion.\u003c/p\u003e\u003cp\u003eChanges in the meibomian glands are often associated with dry eye disease. Few studies have examined the meibomian glands in individuals with no obvious eyelid or ocular surface disorders. For example, the study by Arita et al.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e demonstrated changes in the meibomian glands, as detected by non-contact meibography, increased with age and appeared earlier in males than in females. Moreover, another study by Srivastav, et al.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e revealed that morphological abnormalities of the meibomian glands, such as distortion, tortuosity, hooking, overlapping, abnormal gaps, dropout, and shortened glands, can also be observed in healthy individuals. However, no studies have examined whether alterations in the meibomian glands, eyelid characteristics, and ocular surface condition occur in individuals who do not have dry eye disease.\u003c/p\u003e\u003cp\u003eTherefore, it is interesting to investigate the morphological and functional changes of meibomian glands in asymptomatic individuals and to determine the extent of meibomian gland changes in those without dry eye disease. Understanding these early gland changes in non-dry eye patients is crucial, as they could represent a preliminary stage in the progression toward dry eye disease. By recognizing and potentially managing these meibomian gland alterations early, there may be an opportunity to preserve long-term eye health, maintain optimal tear film stability, and prevent future dry eye symptoms. This evolving perspective on meibomian gland changes in non-dry eye individuals opens the door to new approaches in proactive ocular care and sheds light on the complexity of tear film and eyelid health.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Design\u003c/h2\u003e\u003cp\u003eThis was a cross-sectional study aimed at examining the morphological and functional changes in meibomian glands among 60 non-dry-eye individuals. The study adhered to the principles of the Declaration of Helsinki and received approval from the Committee for the Protection of Human Participants in Research at the Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand (COA no. Si 367/2022). Informed consent was obtained from all subjects prior to enrollment.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eThis study recruited 60 healthy volunteers, aged between 31 and 60 years. Participants were stratified into three age groups (31\u0026ndash;40, 41\u0026ndash;50, 51\u0026ndash;60), with each group consisting of 20 individuals. The focus of our study centered on subjects without dry eye symptoms, identified through Dry Eye-Related Quality of Life scores (DEQS) registering at 14 or lower\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. To ensure the exclusion of other factors that could potentially influence meibomian gland function and dry eye symptoms, exclusion criteria include individuals with eye conditions e.g., dry eye, infections, recent eye surgery, previous refractive surgery, systemic diseases affecting the eyes, regular eye drop or artificial tears use, contact lens wear, recent experimental drug use, recent treatments for MGD, and recent use of certain anti-inflammatory medications.\u003c/p\u003e\n\u003ch3\u003eStudy Procedures\u003c/h3\u003e\n\u003cp\u003eThe examination proceeded sequentially, starting with the measurement of lipid layer thickness (LLT) using LipiView\u0026trade; II Ocular Surface Interferometer, followed by slit-lamp observation of lid margin abnormalities and corneal surface staining using the Modified Oxford Scale. Subsequently, three consecutive measurements of FTBUT were conducted. Tear film production was evaluated using the Schirmer test without a topical anesthetic. The meibomian glands in the upper and lower eyelids were observed using noncontact meibography via the LipiView\u0026trade; II Ocular Surface Interferometer and then converted to meiboscore. The meiboscore grades the extent of meibomian gland loss as follows: 0 indicates no loss; 1 represents loss of less than one-third of the eyelid length; 2 denotes loss between one-third and less than two-thirds; and 3 signifies loss exceeding two-thirds of the eyelid length\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Lastly, a meibomian gland expressibility and meibum quality assessment was performed by pressing the eyelids with a meibomian gland evaluator. All examinations were completed the same day by a single investigator. Detailed descriptions of the outcome measurements are provided in the \u003cb\u003eSupplement\u003c/b\u003e.\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eData were collected from both eyes and statistical analysis was conducted using SPSS version 29 (IBM). Descriptive statistics were reported as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) for normally distributed data and median (IQR) for skewed data. Generalized Estimating Equations (GEE) were employed to compare outcomes among three age groups while adjusting for the correlation between the two eyes. All statistical tests were two-tailed.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAmong the 60 volunteers, 38 were females. All volunteers had no dry eye symptoms, with a DEQS score of 14 or lower. Demographic data including age, sex, and DEQS score in this study were stratified into age groups (31\u0026ndash;40, 41\u0026ndash;50, 51\u0026ndash;60), with an equal distribution of 20 subjects in each age group, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003eAlterations in Meibomian gland morphology, or meibomian gland loss, quantified by meiboscore\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, were observed in both eyelids, with severity increasing with age, as demonstrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, exhibited abnormalities (Meiboscore\u0026thinsp;\u0026ge;\u0026thinsp;1) in 71% of the upper lid and 51% of the lower lid when combining all age groups, with statistically significant differences observed between the three distinct ages (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001 and P\u0026thinsp;=\u0026thinsp;0.04, respectively). Abnormal Meibomian glands (Meiboscore\u0026thinsp;\u0026ge;\u0026thinsp;1) in the upper eyelids were found in 62.5%, 70%, and 80% of individuals aged 31\u0026ndash;40, 41\u0026ndash;50, and 51\u0026ndash;60 years, respectively. Similarly, lower eyelid abnormalities were observed in 37.5%, 47.5%, and 67.5% of individuals in the same age groups, respectively. Most subjects exhibited abnormal meibomian gland morphology in both the upper and lower eyelids.\u003c/p\u003e\u003cp\u003eLid margin abnormalities were identified (Grade1-3 in supplement) in all age groups of healthy volunteers, including characteristics such as margin telangiectasia, meibomian gland plugging, and lid irregularity with frequencies of 82%, 84%, and 12%, respectively. These findings demonstrated that such abnormalities can occur even in individuals without dry eye symptoms. Notably, among lid margin abnormalities, only lid irregularity demonstrated a statistically significant difference among the various age groups (P\u0026thinsp;=\u0026thinsp;0.01) as shown \u003cb\u003ein\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003eRegarding tear function evaluation, the median Schirmer I test was recorded at 10 mm (P25\u0026thinsp;=\u0026thinsp;3.2, P75\u0026thinsp;=\u0026thinsp;29.7), while the median FTBUT was 5.04 seconds (P25\u0026thinsp;=\u0026thinsp;3.71, P75\u0026thinsp;=\u0026thinsp;7.61). In particular, the Schirmer I test revealed a significant difference between the age groups (P\u0026thinsp;=\u0026thinsp;0.015).\u003c/p\u003e\u003cp\u003eFor the thickness of the lipid layer, there were several parameters, including average, minimal and maximal LLT, as shown in the Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The average LLT for all age groups was 61\u0026thinsp;\u0026plusmn;\u0026thinsp;20 \u0026micro;m. In the 51\u0026ndash;60 age group, the average minimal LLT measured 44 \u0026micro;m, showing a significant decrease compared to the 41\u0026ndash;50 age group, where the average was 54 \u0026micro;m (P\u0026thinsp;=\u0026thinsp;0.03).\u003c/p\u003e\u003cp\u003eAnalysis of corneal staining using the Oxford scheme indicated abnormalities with 23.3% and 1.7% presenting at grade 1 and grade 2, respectively. Furthermore, assessments of expressibility and meibum quality demonstrated abnormalities in 66% and 65% of cases, respectively, within the study cohort, as shown \u003cb\u003ein\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, notable anatomical and functional changes in the meibomian glands were observed among non-dry eye populations aged 30-60 years. Additionally, abnormalities of the lid margin, such as telangiectasia, meibomian gland plugging, and irregularities, were also demonstrated. As in the results, more than half of the subjects had anatomical lid abnormalities and meibomian gland loss in both the upper and lower eyelids. Meibomian gland loss, lid irregularity, Schirmer I test, and minimum LLT were found to change significantly with age. Although individuals do not report symptoms of dry eyes, there is evidence of meibomian gland and eyelid abnormalities, which tend to show an increasing trend with advancing age.\u003c/p\u003e\n\u003cp\u003eOur results were compatible with a previous study by Arita et al\u003csup\u003e10\u003c/sup\u003e, which provided a large-scale analysis of meibomian gland changes, focusing on abnormalities in the general population. Meibomian gland dropout was observed in 55% of eyes across an age range of 21 to 93 years, showing a significant association with aging in both males and females. The present study demonstrated a significant increase in meibomian gland loss with age, with abnormal meibomian glands (Meiboscore \u0026ge;1) observed more frequently in the upper eyelids (71%) than in the lower eyelids (51%). Some imaging studies have revealed similar results to ours as they found a higher prevalence of meibomian gland dropout in the upper eyelids\u003csup\u003e11,13\u003c/sup\u003e, while others have reported more gland alterations in the lower eyelids\u003csup\u003e14\u003c/sup\u003e. This inconsistency is speculated to result from variations in anatomical, functional, and mechanical factors of each individual.\u003c/p\u003e\n\u003cp\u003eThe current study specifically focused on individuals (age ranged between 30-60 years) who did not have any dry eye symptoms. A notable number of characteristic meibomian gland changes were still found in these subjects. As we kwow, the tear film lipid layer, primarily derived from the meibomian glands, is essential for tear stability, reducing evaporation, and protecting the ocular surface\u003csup\u003e15\u003c/sup\u003e. LLT was found to be positively correlated with tear breakup time\u003csup\u003e16-18\u003c/sup\u003e. Previous studies have reported normal LLT values ranging from 42 to 88 nm\u003csup\u003e19-22\u003c/sup\u003e, with most healthy individuals exhibiting LLT around\u0026nbsp; 60-80 nm.\u003csup\u003e23\u003c/sup\u003e This values can vary depending on measurement methods, age, ethnicity, and environmental factors\u003csup\u003e24\u003c/sup\u003e. In our study, the mean LLT range was 57-63 nm, which may explain why all subjects reported no dry eye symptoms. Interestingly, the participants in this study could maintain normal LLT, tear break-up time (TBUT), and Schirmer test results despite more than 50% of subjects exhibiting meibomian gland loss and reduced meibum expressibility. The compensatory capacity of the remaining meibomain glands might allow them to maintain secretory function to a certain threshold, beyond which their function becomes evident, manifesting as a short FTBUT, dry eye symptoms, and ocular surface staining. However, LLT showed a declining trend with age, corresponding to the progression of meibomian gland loss, particularly evident in the 51-60 year old group across all parameters. These findings suggested that MGD may develop subclinically before symptoms becomes apparent.\u003c/p\u003e\n\u003cp\u003eThe loss of meibomian glands in both the upper and lower eyelids is associated with thinner lipid layers\u003csup\u003e25,26\u003c/sup\u003e. As mentioned earlier, we found lower meiboscores in the lower eyelids of a non-dry eye population, aligning with previous research suggesting that MGD tends to be less severe in the lower lids compared to the upper lids\u003csup\u003e27\u003c/sup\u003e. This may have a unique relationship with dry eye symptoms\u003csup\u003e25,26\u003c/sup\u003e, possibly explaining the absence of symptoms in these individuals, contrasting with symptomatic populations where lower lid meibomian gland loss is more pronounced. These findings underscore the importance of regional differences in meibomian gland loss and their potential role in the development of dry eye symptoms. Further research is warranted to clarify these relationships and their clinical implications.\u003c/p\u003e\n\u003cp\u003eRegarding lid irregularity, it was found to be less prevalent, with only 10% of subjects exhibiting this feature, suggesting relatively intact lid morphology in the study population. In a study conducted by M. Ha et al\u003csup\u003e25\u003c/sup\u003e, the correlation between lid margin irregularities and meibomian gland loss was examined using infrared-meibography in patients diagnosed with dry eye disease. They found that only irregularities in the lid margin were associated with meibomian gland dropout. In comparison, our study, which focused on a non-dry eye population, also observed much lower prevalence of lid margin irregularities. Therefore, lid margin irregularity may be considered a significant marker for determining MGD severity in symptomatic patients, rather than in the general population.\u003c/p\u003e\n\u003cp\u003eTo the best of our knowledge, this is the first study to analyze meibomian gland characteristics specifucally focus on a non-dry eye population. The findings reveal distinct morphological changes in the meibomian glands, even among individuals without dry eye symptoms. Despite these gland abnormalities, lipid tear film function appeared to be preserved, as reflected by normal LLT values. This observation emphasizes the nature of ocular surface health and underscores the possibility of a dissociation between MG features and other components of tear film dynamics in individuals without overt dry eye symptoms.\u003c/p\u003e\n\u003cp\u003eThis study has some limitations. First, the non-dry eye population examined in this study may not fully represent the diversity of the broad population, as the sample size was relatively modest and limited to a single ethnic group, thereby restricting the generalizability of the findings to other ethnicities. In addition, participant age was confined to 30\u0026ndash;60 years. Individuals within this age group may share similar behaviors, activities, and lifestyle factors, which may not accurately reflect the characteristics of younger or older populations. Lastly, as a cross-sectional study, the findings capture only a single time point, leaving the long-term progression and outcomes of meibomian gland changes unexamined. These aspects highlight opportunities for future research, particularly longitudinal studies, to better elucidate the progression and significance of the observed findings.\u003c/p\u003e\n\u003cp\u003eIn conclusion, this study identified notable meibomian gland abnormalities in individuals without dry eye symptoms, correlating with age. This draws attention to consider age-related variations in interpreting the health of the meibomian glands. Moreover, the findings suggest that the meibomian gland changes can occur even in the absence of dry eye symptoms, highlighting the potential need for early awareness and consideration of preventing interventions to halt disease progression. Further cohort studies are required to better understand these findings and to explore effective strategies for managing and slowing the progression of meibomian gland changes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eConflict of interest:\u003c/h2\u003e\u003cp\u003eNo conflicting relationship exists for any author.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis study was funded by the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, Grant number: R016231048.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eKengpunpanich S. interpreted and analysed of data, wrote the main manuscript text and approved the submitted versionPrabhasawat P. created and designed of the research work, and interpreted of dataJongpipatchai R. prepared figures 1 and Table1,2, collected and analysed the dataChirapapaisan C. designed of the research work , wrote the main manuscrip and approved the submitted versionNgowyutagon P. and Booranapong W. approved the submitted versionAll authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTomlinson, A. et al. The international workshop on meibomian gland dysfunction: report of the diagnosis subcommittee. Invest Ophthalmol Vis Sci,52, 2006\u0026ndash;2049 (2011).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNichols, K. K. et al. The International Workshop on Meibomian Gland Dysfunction: Executive Summary. Invest Ophthalmol Vis Sci, 52, 1922\u0026ndash;1929 (2011).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAsiedu, K. et al. Meibomian Gland Dysfunction in a Youthful Clinical Sample in Ghana. \u003cem\u003eOptom. Vis. Sci.\u003c/em\u003e \u003cb\u003e95\u003c/b\u003e, 349\u0026ndash;353 (2018).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMathers, W. D. et al. Meibomian gland dysfunction in chronic blepharitis. \u003cem\u003eCornea\u003c/em\u003e \u003cb\u003e10\u003c/b\u003e, 277\u0026ndash;285 (1991).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLemp, M. A. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. \u003cem\u003eCLAO J.\u003c/em\u003e \u003cb\u003e21\u003c/b\u003e, 221\u0026ndash;232 (1995).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMathers, W. D. Ocular evaporation in meibomian gland dysfunction and dry eye. \u003cem\u003eOphthalmology\u003c/em\u003e \u003cb\u003e100\u003c/b\u003e, 347\u0026ndash;351 (1993).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShimazaki, J. et al. Ocular surface changes and discomfort in patients with meibomian gland dysfunction. \u003cem\u003eArch. Ophthalmol.\u003c/em\u003e \u003cb\u003e113\u003c/b\u003e, 1266\u0026ndash;1270 (1995).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBron, A. J. et al. Meibomian gland disease. Classification and grading of lid changes. \u003cem\u003eEye (London England)\u003c/em\u003e. \u003cb\u003e5\u003c/b\u003e (Pt 4), 395\u0026ndash;411 (1991).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFoulks, G. N. \u0026amp; Bron, A. J. Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification, and grading. \u003cem\u003eOcul Surf.\u003c/em\u003e \u003cb\u003e1\u003c/b\u003e, 107\u0026ndash;126 (2003).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eArita, R. et al. Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population. \u003cem\u003eOphthalmology\u003c/em\u003e \u003cb\u003e115\u003c/b\u003e, 911\u0026ndash;915 (2008).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSrivastav, S. et al. Morphologic variants of Meibomian glands: age wise distribution and differences between upper and lower eyelids. \u003cem\u003eFront. Med. (Lausanne)\u003c/em\u003e. \u003cb\u003e10\u003c/b\u003e, 1195568 (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSakane, Y. et al. Development and Validation of the Dry Eye\u0026ndash;Related Quality-of-Life Score Questionnaire. \u003cem\u003eJAMA Ophthalmol.\u003c/em\u003e \u003cb\u003e131\u003c/b\u003e, 1331\u0026ndash;1338 (2013).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen, X. et al. Morphology of Meibomian Glands in a 65-Year-Old Norwegian Population without Dry Eye Disease. \u003cem\u003eJ. Clin. Med.\u003c/em\u003e ;\u003cb\u003e11\u003c/b\u003e(3). (2022).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlsuhaibani, A. H., Carter, K. D., Abr\u0026agrave;moff, M. D. \u0026amp; Nerad, J. A. Utility of meibography in the evaluation of meibomian glands morphology in normal and diseased eyelids. \u003cem\u003eSaudi J. ophthalmology: official J. Saudi Ophthalmological Soc.\u003c/em\u003e \u003cb\u003e25\u003c/b\u003e (1), 61\u0026ndash;66 (2011).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCwiklik, L. Tear film lipid layer: A molecular level view. \u003cem\u003eBiochim. Biophys. Acta\u003c/em\u003e. \u003cb\u003e1858\u003c/b\u003e, 2421\u0026ndash;2430 (2016).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIsreb, M. A. et al. Correlation of lipid layer thickness measurements with fluorescein tear film break-up time and Schirmer's test. \u003cem\u003eEye (Lond)\u003c/em\u003e. \u003cb\u003e17\u003c/b\u003e, 79\u0026ndash;83 (2003).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi, Y. et al. Relationship between lipid layer thickness, incomplete blinking rate and tear film instability in patients with different myopia degrees after small-incision lenticule extraction. \u003cem\u003ePloS one\u003c/em\u003e. \u003cb\u003e15\u003c/b\u003e, e0230119 (2020).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJi, Y. W. et al. Automated Measurement of Tear Film Dynamics and Lipid Layer Thickness for Assessment of Non-Sj\u0026ouml;gren Dry Eye Syndrome With Meibomian Gland Dysfunction. \u003cem\u003eCornea\u003c/em\u003e \u003cb\u003e36\u003c/b\u003e, 176\u0026ndash;182 (2017).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKing-Smith, P. E. et al. Application of a novel interferometric method to investigate the relation between lipid layer thickness and tear film thinning. \u003cem\u003eInvest. Ophthalmol. Vis. Sci.\u003c/em\u003e \u003cb\u003e51\u003c/b\u003e, 2418\u0026ndash;2423 (2010).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcDonald, J. E. Surface phenomena of tear films. \u003cem\u003eTrans. Am. Ophthalmol. Soc.\u003c/em\u003e \u003cb\u003e66\u003c/b\u003e, 905\u0026ndash;939 (1968).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKim, W. J. et al. Lipid layer thickness decrease due to meibomian gland dysfunction leads to tear film instability and reflex tear secretion. \u003cem\u003eAnn. Med.\u003c/em\u003e \u003cb\u003e54\u003c/b\u003e, 893\u0026ndash;899 (2022).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee, Y. et al. Characteristics of dry eye patients with thick tear film lipid layers evaluated by a LipiView II interferometer. \u003cem\u003eGraefes Arch. Clin. Exp. Ophthalmol.\u003c/em\u003e \u003cb\u003e259\u003c/b\u003e, 1235\u0026ndash;1241 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBron, A. J. \u0026amp; Tiffany, J. M. The contribution of meibomian disease to dry eye. \u003cem\u003eOcul Surf\u003c/em\u003e. ;2(2):149\u0026thinsp;\u0026ndash;\u0026thinsp;65. (2004). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S1542-0124(12)70046-6\u003c/span\u003e\u003cspan address=\"10.1016/S1542-0124(12)70046-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 16985755.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJung, J. W. et al. Analysis of Factors Associated With the Tear Film Lipid Layer Thickness in Normal Eyes and Patients With Dry Eye Syndrome. \u003cem\u003eInvest. Ophthalmol. Vis. Sci.\u003c/em\u003e \u003cb\u003e57\u003c/b\u003e, 4076\u0026ndash;4083 (2016).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKorb, D. R. \u0026amp; Blackie, C. A. Meibomian gland diagnostic expressibility: correlation with dry eye symptoms and gland location. \u003cem\u003eCornea\u003c/em\u003e \u003cb\u003e27\u003c/b\u003e, 1142\u0026ndash;1147 (2008).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHa, M. et al. Relationship between eyelid margin irregularity and meibomian gland dropout. \u003cem\u003eOcul Surf.\u003c/em\u003e \u003cb\u003e19\u003c/b\u003e, 31\u0026ndash;37 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGolebiowski, B. et al. Lid margins: sensitivity, staining, meibomian gland dysfunction, and symptoms. \u003cem\u003eOptom. Vis. Sci.\u003c/em\u003e \u003cb\u003e89\u003c/b\u003e, 1443\u0026ndash;1449 (2012).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Demonstrated the demographic characteristics of the study participants.\u003c/p\u003e\n\u003ctable\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\"\u003e\n\u003cp\u003e\u003cstrong\u003eDemographic data\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"99\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" width=\"360\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge group: Number (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"120\"\u003e\n\u003cp\u003e\u003cstrong\u003e31-40 (n=20)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"120\"\u003e\n\u003cp\u003e\u003cstrong\u003e41-50 (n=20)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"120\"\u003e\n\u003cp\u003e\u003cstrong\u003e51-60 (n=20)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003eAge, years, (mean)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"99\"\u003e\n\u003cp\u003e44.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"120\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"120\"\u003e\n\u003cp\u003e43\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"120\"\u003e\n\u003cp\u003e55\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003eFemale, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"99\"\u003e\n\u003cp\u003e38 (63.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"120\"\u003e\n\u003cp\u003e13 (65.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"120\"\u003e\n\u003cp\u003e12 (60.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"120\"\u003e\n\u003cp\u003e13 (65.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003eDEQS (mean)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"99\"\u003e\n\u003cp\u003e4.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"120\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"120\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"120\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003en: number of participants\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Summary of the outcome parameters in patients without dry eyes between age groups.\u003c/p\u003e\n\u003ctable width=\"650\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"150\"\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome measures\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" width=\"322\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge group\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"74\"\u003e\n\u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e\u003cstrong\u003e31-40 (n=40)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e\u003cstrong\u003e41-50 (n=40)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e\u003cstrong\u003e51-60 (n=40)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\" width=\"576\"\u003e\n\u003cp\u003e\u003cstrong\u003eLid characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"74\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u003cstrong\u003eLid telangiectasia\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"74\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 0, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e22 (18.3%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e6 (15.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e10 (25.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e6 (15.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"74\"\u003e\n\u003cp\u003e0.54\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 1, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e39 (32.5%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e18 (45.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e12 (30.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e9 (22.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 2, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e53 (44.2%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e12 (30.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e18 (45.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e23 (57.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 3, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e6 (5.0%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e4 (10.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e2 (5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u003cstrong\u003eMeibomian gland plug\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"74\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 0, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e19 (15.8%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e9 (22.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e5 (12.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e5 (12.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"74\"\u003e\n\u003cp\u003e0.22\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 1, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e64 (53.3%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e24 (60.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e19 (47.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e21 (52.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 2, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e36 (30.0%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e7 (17.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e16 (40.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e13 (32.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 3, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e1 (0.8%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e1 (2.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u003cstrong\u003eLid irregularity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"74\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 0, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e106 (88.2%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e37 (92.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e39 (97.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e30 (75.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"74\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.01*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 1, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e14 (11.8%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e3 (7.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e\u0026nbsp;1 (2.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e10 (25.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 2, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 3, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\" width=\"650\"\u003e\n\u003cp\u003e\u003cstrong\u003eMeibomian expressibility\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 0, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e41 (34.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e14 (35.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e14 (35.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e13 (32.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"74\"\u003e\n\u003cp\u003e0.89\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 1, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e39 (32.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e12 (30.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e12 (30.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e15 (37.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 2, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e36 (30.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e12 (30.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e12 (30.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e12 (30.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 3, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e4 (3.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e2 (5.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e2 (5.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\" width=\"650\"\u003e\n\u003cp\u003e\u003cstrong\u003eMeibum quality\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 0, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e42 (35.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e17 (42.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e16 (40.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e9 (22.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"74\"\u003e\n\u003cp\u003e0.09\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 1, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e59 (49.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e17 (42.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e19 (47.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e23 (57.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 2, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e14 (11.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e4 (10.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e2 (5.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e8 (20.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 3, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e5 (4.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e2 (5.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e3 (7.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u003cstrong\u003eSchirmer I: \u003c/strong\u003e[Median (IQR), mm]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e10 \u003cbr /\u003e (3.2-29.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e25.5 \u003cbr /\u003e (3.2-35.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e12.5 \u003cbr /\u003e (4.0-28.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e7.0 \u003cbr /\u003e (3.0-14.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"74\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.015*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\" width=\"650\"\u003e\n\u003cp\u003e\u003cstrong\u003eLipid layer thickness (LLT)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003eAverage LTT\u003cbr /\u003e [mean \u0026plusmn;SD, \u0026micro;m]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e61 \u0026plusmn; 20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e63 \u0026plusmn; 22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e62 \u0026plusmn; 17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e57 \u0026plusmn; 19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"74\"\u003e\n\u003cp\u003e0.28\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003eMinimum LLT\u003cbr /\u003e [mean \u0026plusmn;SD, \u0026micro;m]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e50 \u0026plusmn; 21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e54 \u0026plusmn; 25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e54 \u0026plusmn; 18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e44 \u0026plusmn; 18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"74\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.03*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003eMaximum LLT\u003cbr /\u003e [Med (IQR), \u0026micro;m]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u0026nbsp;81 \u003cbr /\u003e (68-99)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e83.5 \u003cbr /\u003e (68.2-100.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e82.5 \u003cbr /\u003e (75.0-97.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e78.0 \u003cbr /\u003e (62.5-93.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"74\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e0.54\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003eFTBUT: \u003cbr /\u003e [Median (IQR), sec]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e5.04 \u003cbr /\u003e (3.71-7.61)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e5.32 \u003cbr /\u003e (3.90-6.85)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e4.52 \u003cbr /\u003e (3.46-10.94)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e5.12 \u003cbr /\u003e (4.12-6.95)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"74\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\" width=\"650\"\u003e\n\u003cp\u003e\u003cstrong\u003eOcular surface staining* \u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 0, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e90 (75)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e30 (75.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e31 (77.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e29 (72.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"3\" width=\"74\"\u003e\n\u003cp\u003e0.52\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 1, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e28 (23.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e8 (20.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e9 (22.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e11 (27.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"150\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Grade 2, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e2 (1.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"109\"\u003e\n\u003cp\u003e2 (5.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"105\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Modified Oxford scale\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;n: number of eyes\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Meibomian gland dysfunction, Meibomian gland characteristic change, non-dry eye population","lastPublishedDoi":"10.21203/rs.3.rs-6869046/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6869046/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis prospective cross-sectional study examined morphological and functional changes of the meibomian glands in 60 healthy volunteers without dry eye symptoms, stratified into age groups of 31- 40, 41-50, and 51-60 years. Participants were screened using the DEQS questionnaire (score≤14) and underwent ocular assessments, including slit lamp examination, fluorescein tear breakup time (FTBUT), Schirmer test, lipid layer thickness (LLT), blink quality, meibography, evaluation of meibomian gland expressibility, and meibum quality. The results showed an abnormal morphology of the meibomian gland (Meiboscore ≥1) in 71% of the upper lids and 51% of the lower lids, with significant age-related differences. Lid margin abnormalities, such as telangiectasia (82%) and gland plugging (84%), were common in the normal population, while lid margin irregularity (11%) varied significantly by age. Tear function tests revealed a median Schirmer I score of 10 mm. (P=0.01 between age groups) and FTBUT of 5.04 seconds. LLT averaged 61 ± 20 microns and corneal staining abnormalities, graded using the Oxford scale, were observed in 23.3% (grade 1) and 1.7% (grade 2). Expressibility and meibum quality abnormalities were found in 66% and 65% of the participants, respectively. The study highlights significant age-related degenerative changes in the meibomian gland morphology of individuals without dry eye symptoms. Although the tear film remains preserved, these findings suggest that awareness, along with early detection and treatment of MGD, might be necessary to prevent the onset of symptoms and the development of dry eye disease.\u003c/p\u003e","manuscriptTitle":"Characteristics of the Meibomian gland in a population without dry eye symptoms","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-18 13:00:44","doi":"10.21203/rs.3.rs-6869046/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-26T07:33:36+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-18T09:12:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-18T03:15:55+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-16T17:52:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"309896682815203506226413177485454111458","date":"2025-08-13T16:08:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"236024937818128455215641952412439118272","date":"2025-08-11T11:07:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"39139805857607377120691592930182051819","date":"2025-08-11T00:31:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"166909499631405742983317228248939651693","date":"2025-08-10T18:12:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"293274782734385169138759685898367940715","date":"2025-08-10T15:33:55+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-02T09:34:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"229597873845399965727334907901824309057","date":"2025-07-19T03:41:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"61407577754240110992566833040057526542","date":"2025-07-13T10:20:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-13T08:55:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-13T08:53:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-06-17T06:25:10+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-13T07:03:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-06-13T06:17:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3a476d99-9ee6-4102-8bae-9687c08f1ca8","owner":[],"postedDate":"July 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":51613028,"name":"Health sciences/Health care/Disease prevention"},{"id":51613029,"name":"Health sciences/Medical research/Study design"},{"id":51613030,"name":"Health sciences/Signs and symptoms/Eye manifestations"}],"tags":[],"updatedAt":"2025-12-22T16:08:55+00:00","versionOfRecord":{"articleIdentity":"rs-6869046","link":"https://doi.org/10.1038/s41598-025-27641-2","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-12-16 15:57:17","publishedOnDateReadable":"December 16th, 2025"},"versionCreatedAt":"2025-07-18 13:00:44","video":"","vorDoi":"10.1038/s41598-025-27641-2","vorDoiUrl":"https://doi.org/10.1038/s41598-025-27641-2","workflowStages":[]},"version":"v1","identity":"rs-6869046","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6869046","identity":"rs-6869046","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}