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The role of meibomian gland morphological alterations in the development of dry eye disease in type 2 diabetes.

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To evaluate whether specific meibomian gland morphological features can serve as diagnostic indicators of dry eye disease in patients with type 2 diabetes mellitus. This cross-sectional study included patients with type 2 diabetes mellitus and age-matched healthy controls. All participants underwent a comprehensive ocular surface evaluation, including the ocular surface disease index, tear break-up time, Schirmer's I test, corneal staining, eyelid margin scoring, meibum expressibility assessment, meibography scoring, and evaluation of meibomian gland loss area. Meibomian gland morphology was assessed bilaterally. Dry eye severity was determined based on ocular surface disease index scores, tear break-up time, Schirmer's test results, and corneal staining scores. Correlations between meibomian gland features and ocular surface parameters, age, diabetes duration, and hemoglobin A1c levels were analyzed. Receiver operating characteristic analysis was performed to determine the diagnostic value of specific meibomian gland features for dry eye disease. Dry eye disease was diagnosed in 56.6% of patients with diabetes and 22.6% of controls. Compared with controls, patients with diabetes had significantly higher ocular surface disease index scores, greater corneal staining, worse meibum expressibility, increased meibomian gland loss, and lower tear break-up time and Schirmer values (all p<0.05). Meibomian gland dropout, shortening, tortuosity, distortion, overlapping, ghost glands, and lack of extension to the lid margin were significantly more prevalent in patients with diabetes (p<0.05) and showed significant correlations with age, HbA1c levels, and diabetes mellitus duration. Receiver operating characteristic analysis identified meibomian gland dropout, ghost glands, shortening, and lack of extension to the lid margin as the most predictive morphological features for dry eye disease in patients with diabetes. Type 2 diabetes mellitus is associated with distinct meibomian gland morphological alterations that correlate with both dry eye disease severity and systemic diabetic parameters, suggesting potential diagnostic value.

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  • Research Article
  • Cite Count Icon 45
  • 10.1097/apo.0000000000000327
Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review.
  • Nov 1, 2020
  • Asia-Pacific Journal of Ophthalmology
  • Lisa M Nijm + 4 more

Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review.

  • Research Article
  • Cite Count Icon 1
  • 10.2147/opth.s387760
Predictors for Dry Eye Diseases in Patients with Systemic Sclerosis
  • Oct 17, 2022
  • Clinical Ophthalmology (Auckland, N.Z.)
  • Wipada Laovirojjanakul + 6 more

PurposeTo evaluate the prevalence of dry eye disease (DED) in patients with both limited and diffuse subtypes of systemic sclerosis (SSc) and to determine the predictive factors associated with the occurrence of DED.Patients and MethodsThis was a prospective consecutive cross-sectional study of patients with SSc. Each patient underwent a comprehensive ophthalmological evaluation. The Ocular Surface Disease Index (OSDI) was used to assess the symptoms of DED. Tear break up time (TBUT), Schirmer I and ocular surface staining (OSS) were used for objective tests. Patients were diagnosed DED using the DEW II diagnostic method which included both symptom and objective tests. The collected data of patients with and without DED were compared to find out possible associated factors. Logistic regression analysis was used to determine the effects of these factors.ResultsEighty-four SSc patients (25 limited and 59 diffuse subtypes) were studied. The prevalence of DED in SSc patients was 52.38%. The OSDI, tear break up time (TBUT), Schirmer I and ocular surface staining (OSS) were not significantly different between SSc subtypes. Among the 46 symptomatic patients, DED was noted in 44 (52.38%). Most patients (61.4%) were mixed aqueous deficiency-evaporative dry eye type (both TBUT and Schirmer I test positive). The mean age and the median of disease duration in DED patients were higher than those without DED with statistically significant difference (P = 0.004 and 0.019).ConclusionDED was common in patients with SSc. The predictors for the occurrence of DED were older age and longer disease duration. Therefore, OSDI and objective tests for DED should be evaluated in all SSc patients, particularly those with older age and longer disease duration.

  • Research Article
  • 10.59779/jiomnepal.1423
Clinical and Morphological Evaluation of Meibomian Glands in Dry Eye Disease
  • Dec 31, 2025
  • Journal of Institute of Medicine Nepal
  • Poonam Shrestha + 1 more

Introduction Studies on Meibomian gland morphology and association with dry eyes are not common in our scenario. The objective of this study was to know the clinical pattern and morphology of Meibomian glands and its association with dry eyes.MethodsThis was prospective observational study done in Cornea clinic of Nepal Eye Hospital, Kathmandu, Nepal for a period of one year (December 2022 through December 2023). All the patients aged ≥20 years who were diagnosed with Dry eye disease was included in the study. The study variables included age, sex, Ocular surface disease index (OSDI), Schirmer test, Tear break up time (TBUT), Lissamine staining, Meibomian gland loss, Meibomian secretion and dry eyes severity. Descriptive analysis of data was done using frequencies and percentage and correlation between parameters were done using Pearson's test.ResultsOut of fifty cases of dry eye diseases, there were 24 (48%) male and 26 (52%) female with mean age 46.47 years (SD ± 11.96). Most of the patients presented with grade 2 severity of dry eyes (44%, n=22) and the Meibomian gland loss was mainly grade 3 type (60%, n=30). There was a strong positive correlation (r = 0.621, p &lt; 0.01) between Meibomian gland loss and OSDI Score, also strong positive correlation (r= 0.584, p &lt; .001) Meibomian gland secretion and dry eye severity.ConclusionThe severity of dry eye is positively correlated with Meibomian gland loss and the meibum quality.

  • Research Article
  • Cite Count Icon 4
  • 10.1016/j.ghir.2021.101424
Changes in anterior segment parameters and presence of dry eye disease in patients with acromegaly: A Sirius topography study combined with meibography
  • Aug 4, 2021
  • Growth Hormone &amp; IGF Research
  • Deniz Kilic + 4 more

Changes in anterior segment parameters and presence of dry eye disease in patients with acromegaly: A Sirius topography study combined with meibography

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  • Cite Count Icon 38
  • 10.1016/j.jtos.2018.07.003
Subjective versus objective dry eye disease in patients with moderate-severe thyroid eye disease
  • Jul 7, 2018
  • The Ocular Surface
  • Mohsen Bahmani Kashkouli + 6 more

Subjective versus objective dry eye disease in patients with moderate-severe thyroid eye disease

  • Research Article
  • Cite Count Icon 3
  • 10.1186/s12886-025-04084-x
Clinical characteristics of dry eye patients with thyroid disorders: a cross-sectional study
  • Apr 22, 2025
  • BMC Ophthalmology
  • Yiteng Lu + 9 more

PurposeTo characterize the clinical findings in dry eye disease (DED) patients with thyroid disorders and explore their associations with DED symptoms and signs.MethodsIn this retrospective cross-sectional chart review study, 99 patients who were diagnosed as DED and subjected to thyroid function screening were included. Corneal fluorescein staining (CFS), Schirmer 1 test (S1T), tear meniscus height (TMH), the first noninvasive breakup time (NIBUT-first), the average noninvasive breakup time (NIBUT-avg), and meibomian gland (MG) dropout ratio were tested and their correlations with thyroid function were analyzed.ResultsOverall, the average age and gender distribution of DED patients with or without thyroid disorders were similar (p = 0.391 and 0.804). DED patients with thyroid disorders had shorter NIBUT-first(p < 0.001) and NIBUT-avg( p = 0.0042), and higher MG dropout ratio (p = 0.001). Among thyroid function assessments, elevated levels of anti-thyroid peroxidase antibody (Anti-TPO) and anti-thyroglobulin antibody (Anti-Tg) had significant correlation with reduced NIBUT and increased MG dropout ratio. When either NIBUT-first or MG dropout ratio was used as a predicting factor for thyroid disorders, ROC curve demonstrated a cut-off value of 5.255(NIBUT-first AUC 0.770, sensitivity 85.7%, specificity 58.8%, p < 0.001) and 0.229 (MG dropout ratio AUC 0.784, sensitivity 70.6%, specificity 79.6%, p < 0.001). When combining them together, an AUC area of 0.841(sensitivity 88.2%, specificity 66.2%, p < 0.001) was reached.ConclusionShorter NIBUT and higher MG dropout ratio correlated with abnormally elevated levels of Anti-TPO and Anti-Tg in DED patients. A combination of NIBUT and MG dropout assessment may have diagnostic potential as a predictive biomarker of possible thyroid disorders.

  • Research Article
  • Cite Count Icon 9
  • 10.1016/j.exer.2022.109188
Changes in the tear film and meibomian gland morphology between preclinical dry eye and normal subjects represented by ocular surface disease index scores
  • Jul 14, 2022
  • Experimental Eye Research
  • Asra Fatima + 2 more

Changes in the tear film and meibomian gland morphology between preclinical dry eye and normal subjects represented by ocular surface disease index scores

  • Research Article
  • Cite Count Icon 3
  • 10.4103/1110-161x.212040
Evaluation of disease activity markers in relation to dry eye disease in patients with rheumatoid arthritis
  • Jul 1, 2017
  • Egyptian Rheumatology and Rehabilitation
  • Mohja A El-Badawy + 5 more

PurposeThe aim of this study was to correlate the presence of anti-cyclic citrullinated peptide (anti-CCP) and anti-mutated citrullinated vimentin (anti-MCV) antibodies with rheumatoid disease activity and dry eye disease in patients with rheumatoid arthritis (RA).Patients and methodsA total of 69 patients were evaluated for the activity of RA using the Disease Activity Score (DAS-28), erythrocyte sedimentation rate, and C-reactive protein. We used the Health Assessment Questionnaire-Disability Index to assess functional disability. Anti-CCP and anti-MCV antibodies were measured using enzyme-linked immunosorbent assay technique. We assessed dry eye symptoms using Ocular Surface Disease Index (OSDI) questionnaire. Clinical tests used for dry eye assessment included Schirmer’s test, tear breakup time test, and ocular surface fluorescein staining.ResultsAnti-CCP antibody serum levels significantly correlated with DAS (r=0.46, P=0.036), Schirmer’s test (r=0.40, P=0.038), and ocular surface fluorescein staining (r=0.6, P=0.04). Anti-MCV antibody serum levels correlated with DAS (r=0.5, P=0.04), ocular surface fluorescein staining (r=0.9, P=0.007), and OSDI score (r=0.3, P=0.03). DAS showed a nonsignificant correlation with OSDI score and all tests of dry eye. OSDI score significantly correlated with Schirmer’s test (P=0.036).ConclusionDry eye is the most common ocular manifestation in our investigated patients with RA. Dry eye disease existence is not correlated with disease activity, hence all patients with RA should be regularly examined for dye eye regardless of disease severity. Rheumatologists could use the OSDI questionnaire for screening dry eye disease in patients with RA. The presence of anti-CCP and anti-MCV antibodies may denote the existence of dry eye disease and correlates with RA disease activity.

  • Research Article
  • 10.3329/cbmj.v14i2.83296
Standard Patient Evaluation of Eye Dryness (SPEED) and Ocular Surface Disease Index (OSDI) Scores in Dry Eye Disease Patients
  • Jul 28, 2025
  • Community Based Medical Journal
  • Golam Haider + 4 more

Dry eye disease (DED) is a common multifactorial ocular surface state that affects quality of life. A cross-sectional study was conducted in Bangladesh Eye Hospital and Institute, Dhaka, Bangladesh, between January and December of 2024, to assess the impact of age and gender on the severity of dry eye disease (DED) as determined by Standard Patient Evaluation of Eye Dryness (SPEED) and Ocular Surface Disease Index (OSDI) scores. A total of 200 patients, who exhibited symptoms of dry eye disease (DED), were included in this study. They were asked to complete the SPEED and OSDI questionnaires. SPEED and OSDI scores were analyzed by gender and age groups (25–35, 36–45, 46–55, and 56–65 years). The patients aged between 25 and 65 years (mean age was 46.52 years). Among them, 83 were male and 117 were female (male-female ratio was 1:1.41). Regarding SPEED score, 25–35 years age group having the highest mean score (2.84), which indicates more severe symptoms. Regarding OSDI scores, patients in 36-45 years and 25-35 years age groups exhibited the highest mean scores (1.85±0.71 and 1.80±0.76 respectively). In contrast, older patients (56–65 years age group) demonstrated lower score (1.60±0.79), which indicates variation in symptom severity as individual is ageing. In SPEED scores, female patients had slightly higher mean compared to males (2.66±0.65 vs. 2.79±0.54), although the difference was less pronounced. In OSDI scores, male patients were marginally higher compared to females (1.81±0.79 vs. 1.69±0.70); however, the difference was not significant. Gender and age have a big impact on DED symptoms. Our results signify the need for specialized management plans for DED considering demographic variables. CBMJ 2025 July: vol. 14 no. 02 P:154-157

  • Research Article
  • Cite Count Icon 15
  • 10.1097/md.0000000000003833
In vivo confocal microscopy of meibomian glands in primary blepharospasm
  • Jun 1, 2016
  • Medicine
  • Tong Lin + 1 more

The aim of the study was to evaluate the morphological changes of meibomian glands (MGs) in primary blepharospasm (PBS) by in vivo laser scanning confocal microscopy (LSCM) and to investigate the correlations between clinical data of PBS and LSCM parameters of MGs. This prospective and case–control study recruited 30 consecutive PBS patients and 30 age- and gender-matched healthy controls. After questionnaire assessments of ocular surface disease index (OSDI), Jankovic rating scale, and blepharospasm disability index, all subjects underwent blink rate evaluation, tear film break-up time (TBUT), corneal fluorescein staining (CFS), Schirmer test, MG expressibility, meibum quality, MG dropout, and LSCM examination of the MGs. The main LSCM outcomes included the mean MG acinar area and density, orifice diameter, meibum secretion reflectivity, acinar irregularity, and inhomogeneity of interstice and acinar wall. The PBS patients had significantly higher blink rate, higher OSDI and CFS scores, lower TBUT and Schirmer test value, and worse MG expressibility than the controls (All P < 0.05), whereas meibum quality showed no difference (P > 0.05). The PBS patients showed lower values of MG acinar area, orifice diameter and meibum secretion reflectivity, and higher scores of acinar irregularity and inhomogeneity of interstices than the controls (All P < 0.05). For the PBS patients, the severity of blepharospasm evaluated by JCR scale was strong correlated with MG acinar area (P < 0.001), orifice diameter (P = 0.002), meibum secretion reflectivity (P = 0.002), and MG acinar irregularity (P = 0.013). The MG expressibility was significantly correlated to MG acinar area (P = 0.039), orifice diameter (P < 0.001), and MG acinar irregularity (P = 0.014). The OSDI score was moderate correlated with MG acinar irregularity (P = 0.016), whereas the TBUT value was positively correlated with MG acinar area (P = 0.045) and negatively correlated to MG acinar irregularity (P = 0.016). The CFS score was negatively correlated to MG orifice diameter (P = 0.008). The LSCM provided a noninvasive tool for in vivo histopathologic studies of MGs in PBS patients. The excessive constriction of lid muscles closely related to MG morphological alterations of PBS, which offered a new research approach to interpret the interactional mechanism between dry eye and PBS.

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  • Research Article
  • Cite Count Icon 9
  • 10.1155/2020/3275143
Function and Morphology of the Meibomian Glands Using a LipiView Interferometer in Rotating Shift Medical Staff
  • Aug 17, 2020
  • Journal of Ophthalmology
  • Jing Zhang + 3 more

Purpose To investigate the function and morphology of meibomian glands (MG) in night shift medical staff (MS). Methods Sixty-two eyes of 31 patients in the MS group and 59 eyes of 31 patients in the control group were consecutively enrolled. All participants completed Ocular Surface Disease Index (OSDI) and Standard Patient Dry Eye Evaluation (SPEED) questionnaires for dry eye severity, as well as Schirmer I and tear break-up time (TBUT) tests. LipiView® II Ocular Surface Interferometer was used for lipid layer thickness (LLT), MG dropout, and partial blink (PB) rate tests. MG expression was measured with an MG evaluator. Results The OSDI score in the MS group was 22.39 ± 13.42, which was significantly higher than that in the control group (9.87 ± 6.64 Z = −3.997, P=0.001). The SPEED score in the MS group was 7.94 ± 3.81, which was significantly higher than in the control group (3.65 ± 2.11, Z = −4.766, P=0.001). There was no significant difference in Schirmer I test between the MS group and control group (Z = −1.346, P=0.178). TBUT in MS group was significantly shorter than that in the control group (Z = −5.201, P=0.001). The mean LLT of the MS group was 55.02 ± 21.17 nm significantly thinner than that of the control group 72.76 ± 21.62 nm (Z = −4.482, P=0.001). MG loss occurred in 45.16% of affected eyes in the MS group and 16.13% of affected eyes in the control group, and the difference was statistically significant (χ2 = 14.352, P=0.001). MG yielding liquid secretion and MG yielding secretion score were significantly lower in the MS group than in the control group (Z = −3.641, P=0.001; Z = −3.146, P=0.001, resp.). There was a negative correlation between mean LLT and SPEED score (Spearman r = −0.363, P=0.045). Conclusions Night shift MS had a higher incidence of MGD compared to day workers.

  • Research Article
  • Cite Count Icon 33
  • 10.1097/ico.0000000000002837
TearCare for the Treatment of Meibomian Gland Dysfunction in Adult Patients With Dry Eye Disease: A Masked Randomized Controlled Trial
  • Sep 28, 2021
  • Cornea
  • Preeya K Gupta + 6 more

Purpose:The aim of this study was to demonstrate the safety and effectiveness of a single TearCare procedure compared with a single LipiFlow procedure in treatment of the dry eye disease associated with meibomian gland dysfunction.Methods:In a multicenter, masked, randomized controlled trial, 135 subjects received a single TearCare (TC) treatment (n = 67) or a single LipiFlow (LF) treatment (n = 68) at baseline and were followed up for 1 month posttreatment. Tear film breakup time, meibomian gland function, and corneal and conjunctival staining scores were assessed as dry eye signs at baseline, 2 weeks, and 1 month; dry eye symptoms were assessed using the Ocular Surface Disease Index, Symptom Assessment in Dry Eye, and eye dryness questionnaires at baseline and 1 month.Results:At 1 month posttreatment, both groups demonstrated significant improvements (P < 0.0001) in mean tear film breakup time and meibomian gland secretion score to 3.0 ± 4.4 and 11.2 ± 11.1 in the TC group and 2.6 ± 3.3 and 11.0 ± 10.4 in the LF group, respectively. The mean eye dryness, Symptom Assessment in Dry Eye, and Ocular Surface Disease Index scores were significantly reduced (P < 0.0001) by 35.4 ± 34.1, 38.2 ± 31.0, and 27.9 ± 20.5 in the TC group and 34.9 ± 26.9, 38.0 ± 25.9, and 23.4 ± 17.7 in the LF group, respectively. There were no statistically significant differences for any result between the groups. However, the TC group demonstrated numerically greater improvements consistently in all signs and symptoms. Device-related ocular adverse events were reported in 3 patients in the TC group (superficial punctate keratitis, chalazion, and blepharitis) and 4 patients in the LF group (blepharitis, 2 cases of foreign body sensation, and severe eye dryness).Conclusions:A single TearCare treatment significantly alleviates the signs and symptoms of dry eye disease in patients with meibomian gland dysfunction and is equivalent in its safety and effectiveness profile to LipiFlow treatment as shown in this 1-month follow-up study.

  • Research Article
  • 10.4103/ijo.ijo_608_25
Adjunct Topical Human Immunoglobulin IgG Therapy in Dry Eye Disease.
  • Mar 27, 2025
  • Indian journal of ophthalmology
  • Murugesan Vanathi + 9 more

The aim of this study was to evaluate the role of topical human IgG eye drops (4 mg/mL) as adjunct therapy in eyes with moderate to severe refractory dry eye disease (DED). A prospective, longitudinal, open label, dual cohort study of patients with chronic DED of moderate to severe grade comprise of OSIG therapy group cohort on topical immunoglobulin IgG 0.4% four times daily, as adjunctive therapy for one year, to study the role of OSIG therapy in comparison with conventional treatment. Patients above 18 years of age with chronic moderate to severe grade DED with tear break-up time (TBUT) ≤7 seconds, Schirmer test ≤9 mm/5 minutes, ocular surface disease index (OSDI) score ≥13, National Eye Institute (NEI) corneal staining score >3, and conjunctival staining score >3 were recruited into the study. Study participants in the conventional treatment cohort group were on topical lubricants four hourly (carboxymethyl cellulose 0.5% and lubricant ointment at bedtime), topical steroids (prednisolone 1%/fluorometholone 0.1%/loteprednol 0.5%) therapy as per the severity of the DED requirement and topical immunomodulators (cyclosporine A 0.1% eye drops or tacrolimus 0.1% eye ointment) twice daily. Study participants in the OSIG treatment cohort group were started on topical human immunoglobulin IgG 0.4% four times daily as adjunct therapy in addition to the all the above-mentioned medications for a period of 12 months. Study parameters included DED severity level assessment, NIH score, ocular surface evaluation tests, Schirmer's I test, TBUT, corneal and conjunctival staining score, OSDI score, and conjunctival hyperemia score. Ocular surface imaging using LipiView and ocular surface analyzer imaging for non-invasive TBUT (NITBUT), meibomian gland, and tear imaging was performed for the OSIG treatment cohort. Study characteristics were evaluated at time of recruitment into the study (baseline visit) and at serial follow-up of months 3, 6, and 12 in OSIG treatment group and follow-up at month 6 in conventional treatment group. Treatment grading score was devised in accordance to the frequency of application of lubricants and steroids and potency of steroids. Our study of 71 eyes of 36 patients [mean age 39 ± 11.80 years] in OSIG treatment cohort group and 64 eyes of 32 patients [mean age 40 ± 11.53 years] in conventional treatment cohort group observed a significant reduction in the objective ocular surface symptom assessment parameters of OSDI scores, and dry eye severity level with improvement in clinical assessment parameters of TBUT, ocular surface staining scores, and conjunctival hyperemia grades in eyes on adjunct OSIG treatment cohort as compared to the conventional therapy cohort. The frequency of topical lubricants and steroids along with the potency of steroids used showed a decreasing trend with 45.28% noted to have become free of steroid dependence at the end of 12 months of OSIG therapy. Adjunct topical IgG therapy also enabled the shifting of 37.14% of eyes from higher to lower potency steroids by the end of 12 months of treatment with OSIG therapy. The frequency of administration of lubricants decreased in 83.33% of eyes 12 months follow-up. The success rate determined based on improvement in ocular surface evaluation was 75.76%, treatment scores improved in 74.98%, and symptoms evaluation (OSDI) was 75.76% in the OSIG therapy cohort. Topical immunoglobulin IgG 0.4% as adjunct therapy seems to have a definitive role in reducing topical steroid and lubricant dependency in moderate to severe chronic DED compared to conventional therapy.

  • Research Article
  • 10.1016/j.aopr.2025.01.001
The effect of COVID-19 on visual outcome and dry eye after SMILE.
  • May 1, 2025
  • Advances in ophthalmology practice and research
  • Zhi Fang + 6 more

The effect of COVID-19 on visual outcome and dry eye after SMILE.

  • Research Article
  • Cite Count Icon 103
  • 10.1111/aos.12174
Dry eye disease in French elderly subjects: the Alienor Study
  • Jun 7, 2013
  • Acta Ophthalmologica
  • Florence Malet + 9 more

To describe dry eye disease in French elderly subjects. The Alienor Study is a population-based study on age-related eye disease in 963 residents of Bordeaux (France), aged 73 years or more. Self-reported dry eye disease and use of artificial tears were documented through face-to-face interview. Dry eye symptoms were assessed using the Ocular Surface Disease Index (OSDI) questionnaire and tear film stability by tear break-up time measurements (TBUT). Definite dry eye disease was defined as self-reported dry eye, confirmed by use of artificial tears and/or OSDI greater or equal to 22. Nine hundred and fifteen subjects, with mean age of 80 ± 4 years, returned the OSDI questionnaire. Of these, 271 (29.6%) subjects reported a dry eye disease and 135 (14.7%) were using artificial tears. An OSDI score > 22 was found in 359 (39.2%) subjects and a TBUT < 5 seconds in 335/746 (44.9%) subjects. Overall, definite dry eye affected 21.9% of subjects and was more frequent in women (27.1%) than in men (13.6%). After multivariate adjustment, dry eye disease was also significantly less frequent in subjects with high educational level (odds ratio (OR) = 0.49, 95% confidence interval (CI): 0.31-0.78 for long secondary school) and more frequent in subjects with ocular hypertension (OR = 1.61, 95% CI: 1.02-2.57) and those using anxiolytics (OR = 1.53, 95% CI: 1.02-2.29). This large observational study confirmed the high prevalence of dry eye symptoms among elderly subjects and confirmed some of the previously identified risk factors (in particular female gender and use of anxiolytics).

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