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.

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.

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.

Distinguish between EDE severity levels by analysing the MGLA, conjunctival hyperemia and corneal staining. 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. 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). Severe EDE participants have higher MGLA, conjunctival hyperemia, and corneal staining values than healthy, mild, or moderate EDE participants.

(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.

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. 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|). 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). 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.