Meibum Lipidomic Analysis in Evaporative Dry Eye Subjects.

Meibomian Glands (MG) are sebaceous glands responsible for the production of meibum, the main component of the Tear Film Lipid Layer (TFLL). The TFLL facilitates the spread of the tear film over the ocular surface, provides stability and reduces tear evaporation. Alterations in meibum composition lead to different ocular alterations like Meibomian Gland Dysfunction (MGD) and subsequent Evaporative Dry Eye (EDE). The aim of the present study was to investigate the composition and abundance of meibum lipids and their relationship with eyelid margin abnormalities, lipid layer patterns and MG status. The study utilizes a lipidomic approach to identify and quantify lipids in meibum samples using an Elute UHPLC system. This system considered all four dimensions (mass/charge, retention time, ion mobility and intensity) to provide the accurate identification of lipid species. Samples were categorized as healthy or low/no signs of alteration (group 1) or severe signs of alteration or EDE/MGD (group 2). The current investigation found differences in Variable Importance in Projection lipid abundance between both groups for the MGD signs studied. Changes in meibum composition occur and are related to higher scores in eyelid margin hyperaemia, eyelid margin irregularity, MG orifice plugging, MG loss and lipid layer pattern.

A Comprehensive Study on Tear Meniscus Height Inter-Eye Differences in Aqueous Deficient Dry Eye Diagnosis.

(1) Background: Dry eye disease (DED) is a chronic ocular surface condition that requires precise diagnostic tools. The present study aimed to investigate the diagnostic potential of the absolute inter-eye difference (|OD-OS|) in tear meniscus height (TMH) for the detection of the presence of aqueous deficient dry eye (ADDE). (2) Methods: A sample of 260 participants with dry eye complaints underwent ocular surface examinations thorough diagnostic assessments based on the Tear Film and Ocular Surface Society guidelines (TFOS DEWS II). Participants were subsequently categorized as No ADDE and ADDE based on TMH. Statistical analyses to determine the optimal TMH|OD-OS| cut-off value in a randomly selected study group (200 participants) were performed, while a separate validation analysis of the cut-off value obtained in a random cross-validation group (60 participants) was also performed. (3) Results: The significant diagnostic capability of TMH|OD-OS| (area under the curve = 0.719 ± 0.036, p < 0.001) was found. The identified cut-off value of 0.033 mm demonstrated reliable specificity (77.6%) and moderate sensitivity (59.1%). Cross-validation confirmed the cut-off value's association with the TFOS DEWS II diagnostic criterion (Cramer's V = 0.354, p = 0.006). (4) Conclusions: The present study provides evidence for the diagnostic potential of TMH|OD-OS| in identifying ADDE. The identified cut-off value enhances the specificity and offers moderate sensitivity, providing an objective tool for clinical decision making.

Tear film osmolarity variation between weeks in healthy and dry eye disease subjects / Variação semanal da osmolaridade do filme lacrimal em indivíduos saudáveis e com síndrome do olho seco

ABSTRACT Purpose: The possible variability in diagnostic test results is a statistical feature of dry eye disease patients. The clinician should consider tear film variations over time since the timing of tear film measurements is important for proper diagnosis. The purpose of the present study was to analyze the inter-week variation of osmolarity measurement in healthy and dry eye disease participants. Methods: Based on the Dry Eye Workshop II (DEWS-II) diagnostic methodology report criteria, a battery of tests (Ocular Surface Disease Index [OSDI] questionnaire, breakup time, and corneal staining) was administered to rule out the presence of dry eye disease. A total of 40 qualified volunteers were recruited into two groups: with only 20 healthy and 20 dry eye disease participants. The inter-week variation of osmolarity in the two groups was measured using a TearLab osmometer in two sessions one-week apart. The differences between the results were calculated. Results: There were no significant differences in osmolarity between the two sessions for either the healthy (paired t-test; p=0.085) or dry eye disease (paired t-test; p=0.093) participants. Moreover, there was no significant correlation between the means and differences in either session on healthy (Pearson correlation: r=0.020; p=0.935) or dry eye disease (Pearson correlation: r=-0.022; p=0.928) participants. In session 1, there was a significant difference in osmolarity values between groups (unpaired t-test; p=0.001), but no difference was found in session 2 (unpaired t-test; p=0.292). Conclusions: The present study discovered no inter-week variation in the tear film osmolarity of healthy and dry eye disease participants classified based on the DEWS-II criteria.

RESUMO Objetivo: A possível variabilidade nos resultados de testes diagnósticos é uma característica estatística dos pacientes com síndrome do olho seco. O médico deve considerar as variações do filme lacrimal ao longo do tempo, pois o momento em que o filme lacrimal é medido pode ser crítico para o diagnóstico adequado. O objetivo deste estudo foi analisar a variação semanal da osmolaridade do filme lacrimal em participantes saudáveis e em outros com síndrome do olho seco. Métodos: Com base nos critérios da metodologia de diagnóstico do relatório da Dry Eye Workshop II (DEWSII), foi aplicada uma bateria de testes (questionário do índice de doença da superfície ocular [OSDI], tempo de ruptura do filme lacrimal e coloração da córnea) para descartar a presença de síndrome do olho seco. Um total de 40 voluntários qualificados foi recrutado e distribuído em dois grupos de 20 participantes saudáveis e 20 participantes com síndrome do olho seco. A variação da osmolaridade entre semanas foi medida com um osmômetro TearLab em duas sessões com uma semana de intervalo nos dois grupos. As diferenças entre os resultados foram então calculadas. Resultados: Não foram encontradas diferenças significativas na osmolaridade entre as medidas obtidas nas duas sessões, nem no grupo de participantes saudáveis (teste de t pareado; p=0,085), nem no de participantes com síndrome do olho seco (teste de t pareado; p=0,093). Não foi detectada nenhuma correlação significativa entre as médias e diferenças entre as duas sessões entre participantes saudáveis (correlação de Pearson: r=0,020, p=0,935) e aqueles com síndrome do olho seco (correlação Pearson: r=-0,022, p=0,928). Foi encontrada uma diferença significativa nos valores de osmolaridade entre os dois grupos na primeira sessão (teste de t não pareado; p=0,001), mas nenhuma diferença foi encontrada na segunda sessão (teste de t não pareado; p=0,292). Conclusões: O presente estudo não encontrou variação entre semanas consecutivas na osmolaridade do filme lacrimal em participantes saudáveis e com síndrome do olho seco, classificados com base nos critérios do DEWSII.

Capability of the Inter-Eye Differences in Osmolarity, Break-Up Time and Corneal Staining on the Diagnostic of Dry Eye.

PURPOSE: Inter-eye variability is a recognized characteristic of Dry Eye Disease (DED) and has been proposed as a diagnostic indicator in clinical practice. This study aimed to assess the diagnostic potential of the absolute difference between eyes in three key diagnostic tests recommended by the Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) Diagnostic Methodology report: tear film osmolarity, Fluorescein Break-Up Time (FBUT), and ocular surface staining. METHODS: A total of 180 participants were included in a cross-sectional study. Before a dry eye examination, participants completed an online self-administered OSDI questionnaire. The TFOS DEWS II diagnostic criteria for DED assessment were used: along with OSDI, osmolarity, FBUT and ocular surface staining were measured in all participants in both eyes following standardized methodology. Based on signs and symptoms, participants were diagnosed as having No DED or DED. After diagnosis, the parameters were computed as the right and left eyes' absolute inter-eye difference (|OD-OS|). RESULTS: Receiver Operating Characteristics analyses for computed parameters were used based on the previous diagnosis. ROC analyses showed that Osmolarity|OD-OS| have a diagnostic capability to differentiate between No DED and DED participants with a cut-off value of 9.5 mOsm/L (AUC = 0.745 ± 0.052, p < 0.003), whereas FBUT|OD-OS| and Corneal Stainning|OD-OS| have not (AUC, both p ≥ 0.160). CONCLUSION: The present study found that the Osmolarity|OD-OS| parameter could be used as a diagnostic indicator for DED assessment, while the FBUT|OD-OS| and the Corneal Staining|OD-OS| parameters do not have this capability.

Intraocular Pressure Fluctuation Throughout the Day.

Purpose To compare intraocular pressure (IOP) values at different time points, both in the total sample and according to iridocorneal angle aperture, to assess whether IOP fluctuations were constant throughout the day, and to examine correlations with other factors. Methods Over a single day, the IOP of 34 volunteers was measured at three-hour intervals from 9:00 a.m. to 6:00 p.m. To avoid any IOP value being affected by other measurements, anamnesis, slit-lamp evaluation (with iridocorneal angle measurement), and refractive status were performed after the final measurement. The differences between IOP values at different time points and IOP fluctuation at three-hour intervals were compared by ANOVA and Friedman test, respectively, both for the total group and according to iridocorneal angle aperture. For relationships, Pearson's correlation was performed for parametric variables and Spearman's correlation for nonparametric variables. Results Significant differences were observed in IOP between time points for the total sample (p < 0.001), but not for a narrow-angle group (p = 0.058). No significant differences were found in IOP fluctuations at three-hour intervals either in the total sample or according to angle aperture (all p ≥ 0.332). There was a positive correlation of IOP at different time points (all r ≥ 0.646, all p < 0.001) but no relationship with spherical equivalent, age, or sleep duration (all p ≥ 0.057). IOP at 12:00 p.m. was correlated with a 12:00 p.m. to 3:00 p.m. fluctuation (r = 0.428, p = 0.012); and IOP fluctuation between 9:00 a.m. and 12:00 p.m. was correlated with age (r = 0.485, p = 0.004). Conclusion As IOP decreases from morning until at least 6:00 p.m., measuring these two values during clinical evaluation is essential for the effective monitoring and prevention of IOP-related diseases.

Meibomian gland secretion quality association with ocular parameters in university students during COVID- 19 restrictions.

PURPOSE: To determine if the Meibomian Gland (MG) secretion quality is associated with symptoms of ocular discomfort, hours of Video Display Terminals (VDT) use, eyelid margin abnormalities, conjunctival hyperemia, and Meibomian Gland Loss Area (MGLA) in a sample of university students. METHODS: An online survey that included an Ocular Surface Disease Index (OSDI) questionnaire and an extra question about hours of VDT use recruited an initial sample of 183 participants. Only 120 participants that fulfilled the inclusion criteria were scheduled for a battery of ocular surface and MG specific exam. The tests include: 1) meibometry, 2) slit lamp exploration of eyelid margin abnormalities (irregularity, hyperemia and MG orifices plugging), MG secretion quality and conjunctival hyperemia, and 3) Meibography. RESULTS: Significant positive correlations between the MG secretion quality and eyelid margin hyperemia, MG orifices plugging, MGLA, nasal conjunctival hyperemia, and temporal conjunctival hyperemia (Spearman Rho; all r>0.186, p<0.042) were found. Multivariate regression found association between OSDI with hours of VDT use (B=0.316, p=0.007), and eyelid hyperemia (B=0.434, p≤ 0.001). A statistical association between MG secretion quality and eyelid margin hyperemia, MG orifices plugging, MGLA and conjunctival hyperemia (Fisher's exact; all p<0.039) were found. Multivariate regression found association between MG secretion quality with MG orifices plugging (B=0.295, p=0.004) and meibometry (B=-0.001, p=0.029). CONCLUSION: Participants with higher values in MG secretion quality have higher values in eyelid margin hyperemia, MG plugging, MGLA, and conjunctival hyperemia. No direct relationship between MG secretion quality and hours of VDT use or OSDI were found.

A cross-sectional study of non-modifiable and modifiable risk factors of dry eye disease states.

PURPOSE: The present study aimed to determine the relationship of non-modifiable (rheumatoid arthritis, thyroid diseases, and arterial hypertension) and modifiable risk factors (diuretics, antidepressants, or anxiolytics tranquilizers) with the different Dry Eye Disease (DED) diagnostics in a sample adjusted by antihistamines intake. METHODS: A total of 400 participants were included in a cross-sectional study. Before a dry eye examination, participants completed an online self-administered OSDI questionnaire with six additional questions about possible DED risk factors. The Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS-II) diagnostic criteria of DED was used. Based on signs and/or symptoms, participants were divided into 4 groups: No DED, Pre-clinical DED, Predisposition to DED and DED. Since the symptom scores would have been altered by the use of antihistamines, the analysis of each outcome was adjusted for this factor, where those participants were assumed to be symptomatic. RESULTS: Multivariable logistic regression found thyroid disease as a possible risk factor for DED (OR 4.53, 95 % CI 1.04-19.73; Fisher's exact, p = 0.044; Cramers V = 0.140, p = 0.024). No association was found between the studied parameters and Pre-clinical DED (Fisher's exact, all p ≥ 0.398; Cramers V, all p ≥ 0.242) or Predisposition to DED (Fisher's exact, all p ≥ 0.065; Cramers V, all p ≥ 0.031). CONCLUSION: Participants with thyroid disease were more likely to develop DED, therefore, thyroid disease could be a risk factor for DED.

Analysis of the Differences in Ocular Surface Damage and Inflammatory Signs between Healthy and Evaporative Dry Eye Participants.

OBJECTIVE: Distinguish between EDE severity levels by analysing the MGLA, conjunctival hyperemia and corneal staining. METHODS: One hundred participants were recruited based on OSDI, TO, TFBUT, TMH, and LLP to be categorised as healthy (Group 1) or EDE (Group 2). Group 2 was divided into Group 2A (mild symptoms), 2B (moderate), and 2C (severe). MGLA, conjunctival hyperemia, and corneal staining were measured. RESULTS:  Positive correlation between MGLA, conjunctival hyperemia, and corneal staining were found (all r ≥ 0.221, p ≤ 0.027). Significant differences were found: MGLA between Group 1 vs. 2C and 2C vs. 2A or 2B; conjunctival hyperemia between Group 1 vs. 2A, 2B or 2C; corneal staining between Group 1 vs. 2B or 2C and 2A vs. 2B or 2C (all p ≤ 0.049). CONCLUSION: Severe EDE participants have higher MGLA, conjunctival hyperemia, and corneal staining values than healthy, mild, or moderate EDE participants.

Diurnal variations of tear film osmolarity on the ocular surface.

The measurement of tear film osmolarity has been suggested as a gold standard in the diagnosis of dry eye. Many tear film physiological variables oscillate during the day. This review summarises current clinical knowledge regarding diurnal osmolarity variation in the tear film. A critical analysis is presented in respect of of sample size and characteristics, differences in the diurnal osmolarity variation on healthy versus altered tear film conditions or environment, and time of day and number of measurements undertaken. A comparison of 21 studies was made for studies in which one of the main objectives was to analyse the variance of tear film osmolarity at different time-points in a day on human cohorts. Tear film osmolarity appeard to be somewhat influenced by the time of day in healthy subjects and patients with ocular surface disease, or altered by environmental conditions. Both healthy and non-physiological tear film cohorts showed variations in results depending on the study: no variations during the day or statistically different values at some point in the day. These differences could be in the middle of the day or between the beginning and the end of the day, with higher values in the morning than in the afternoon, or even the opposite situation. The possibility of diurnal variations in tear film osmolarity should be considered by the clinician since the time of day when the tear film measurements are made can be critical in making the right diagnosis. Future studies in the diurnal variation field may have to use a well-established range of measurement time-points and a larger group of healthy subjects and and subjects who have a tear film altered by pathological or environmental conditions.

Categorization of the Aqueous Deficient Dry Eye by a Cut-Off Criterion of TMH Measured with Tearscope.

A decrease of the Tear Meniscus Height (TMH) has been proposed as a useful indicator for Aqueous Deficient Dry Eye (ADDE) categorization. The present study aimed to calculate a TMH cut-off criterion for the categorization or severity assessment of ADDE with the Tearscope. 200 participants with a previous Dry Eye Disease (DED) diagnosis according to TFOS DEWS-II criteria were recruited. TMH by slit-lamp illumination and Lipid Layer Pattern (LLP) with Tearscope were assessed to categorise the participants into the ADDE or the Evaporative Dry Eye (EDE) group. The ADDE group was also subdivided into Mild-moderate ADDE and Moderate-severe ADDE based on TMH with slit-lamp. Additionally, the TMH was measured by Tearscope (TMH-Tc). Receiver Operating Characteristics showed that the TMH-Tc have a diagnostic capability to differentiate between ADDE and EDE participants, and between Mild-moderate or Moderate-severe ADDE, with a cut-off value of 0.159 mm (AUC = 0.843 ± 0.035, p < 0.001; sensitivity: 86.4%; specificity: 75.4%) and 0.105 mm (AUC = 0.953 ± 0.025, p < 0.001; sensitivity: 98.1%; specificity: 80.0%), respectively. The present study proposed a cut-off criterion to differentiate between ADDE and EDE participants, or between ADDE severities through TMH assessed by Tearscope.