A surface-engineered contact lens for tear fluid biomolecule sensing.

The eyes provide rich physiological information and offer diagnostic potential as a sensing site, and probing tear constituents via the wearable contact lens could be explored for healthcare monitoring. Herein, we propose a novel adhesive contrast contact lens platform that can split tear film by natural means of tear secretion and blinking. The adhesive contrast is realized by selective grafting of a lubricant onto a polydimethylsiloxane (PDMS)-based contact lens, leading to high pinning zones on a non-adhesive background. The difference in contact angle hysteresis facilitates the liquid splitting. Further, the method offers control over the droplet volume by controlling the zone dimension. The adhesive contrast contact lens is coupled with fluorescent spectroscopic as well as colorimetric techniques to realize its potential as a diagnostic platform. The adhesive contrast contact lens is exploited to detect the level of lactoferrin in tear by sensitizing split droplets with Tb3+ ions. The adhesive contrast contact lens integrated with a fluorescence spectrometer was able to detect the lactoferrin level up to a concentration of 0.25 mg mL-1. Additionally, a colorimetric detection based on the fluorescence of the lactoferrin-terbium complex is demonstrated for the measurement of lactoferrin, with a limit of detection in the physiological range up to 0.5 mg mL-1.

In-depth correlation analysis between tear glucose and blood glucose using a wireless smart contact lens.

Tears have emerged as a promising alternative to blood for diagnosing diabetes. Despite increasing attempts to measure tear glucose using smart contact lenses, the controversy surrounding the correlation between tear glucose and blood glucose still limits the clinical usage of tears. Herein, we present an in-depth investigation of the correlation between tear glucose and blood glucose using a wireless and soft smart contact lens for continuous monitoring of tear glucose. This smart contact lens is capable of quantitatively monitoring the tear glucose levels in basal tears excluding the effect of reflex tears which might weaken the relationship with blood glucose. Furthermore, this smart contact lens can provide an unprecedented level of continuous tear glucose data acquisition at sub-minute intervals. These advantages allow the precise estimation of lag time, enabling the establishment of the concept called 'personalized lag time'. This demonstration considers individual differences and is successfully applied to both non-diabetic and diabetic humans, as well as in animal models, resulting in a high correlation.

Dissociation Kinetics and Antimicrobial Activity of Ofloxacin Antibiotic in Artificial Tears Via 1H-NMR, Raman, and UV-Vis Spectroscopic Analysis.

Introduction: The hydrogen-bonded networks play a significant role in influencing several physicochemical properties of ofloxacin in artificial tears (ATs), including density, pH, viscosity, and self-diffusion coefficients. The activities of the ofloxacin antibiotic with Ats mixtures are not solely determined by their concentration but are also influenced by the strength of the hydrogen bonding network which highlight the importance of considering factors such as excessive tear production and dry eye conditions when formulating appropriate dosages of ofloxacin antibiotics for eye drops. Objectives: Investigating the physicochemical properties of ofloxacin-ATs mixtures, which serve as a model for understanding the impact of hydrogen bonding on the antimicrobial activity of ofloxacin antibiotic eye drops. Determine the antimicrobial activities of the ofloxacin-Ats mixture with different concentration of ofloxacin. Methods: The ofloxacin-ATs mixtures were analyzed using 1H-NMR, Raman, and UV-Vis spectroscopies, with variation of ofloxacin concentration to study its dissociation kinetics in ATs, mimicking its behavior in human eye tears. The investigation includes comprehensive analysis of 1H-NMR spectral data, self-diffusion coefficients, Raman spectroscopy, UV-Vis spectroscopy, liquid viscosity, and acidity, providing a comprehensive assessment of the physicochemical properties. Results: Analysis of NMR chemical shifts, linewidths, and self-diffusion coefficient curves reveals distinct patterns, with peaks or minima observed around 0.6 ofloxacin mole fraction dissociated in ATs, indicating a strong correlation with the hydrogen bonding network. Additionally, the pH data exhibits a similar trend to viscosity, suggesting an influence of the hydrogen bonding network on protonic ion concentrations. Antibacterial activity of the ofloxacin-ATs mixtures is evaluated through growth rate analysis against Salmonella typhimurium, considering varying concentrations with mole fractions of 0.1, 0.4, 0.6, 0.8, and 0.9. Conclusions: The antibiotic-ATs mixture with a mole fraction of 0.6 ofloxacin exhibited lower activity compared to mixtures with mole fractions of 0.1 and 0.4, despite its lower concentration. The activities of the mixtures are not solely dependent on concentration but are also influenced by the strength of the hydrogen bonding network. These findings emphasize the importance of considering tear over-secretion and dry eye problems when designing appropriate doses of ofloxacin antibiotics for eye drop formulations.

New Insights into the Molecular Structure of Tear Film Lipids Revealed by Surface X-ray Scattering.

The tear film lipid layer (TFLL) is a unique biological membrane that serves a pivotal role in the maintenance of ocular surface health. Reaching an overarching understanding of the functional principle of the TFLL has been hampered by a lack of insights into the structural and functional roles played by individual lipid classes. To bridge this knowledge gap, we herein focus on studying films formed by principal lipid classes by surface scattering methods. Through grazing incidence X-ray diffraction and X-ray reflectivity studies, we reveal quantitative data about the lattice distances, molecular tilt angles, and mono/multilayer thickness and density profiles for central TFLL lipid classes under close to simulated physiological conditions. In addition, we discuss the correlation of the results to those obtained previously with the natural lipid composition of meibum.

Multi-biomarker combination detection system for diagnosis and classification of dry eye disease by imaging of a multi-channel metasurface.

Dry eye disease (DED) is one of the most common ocular surface diseases, characterized by unstable tear film and ocular inflammation, affecting hundreds of millions of people worldwide. Currently, the clinical diagnosis of DED mainly relies on physical methods such as optical microscopy and ocular surface interferometric imaging, but classifying DED is still difficult. Here, we propose a compact and portable immune detection system based on the direct imaging of a nanophotonic metasurface with gradient geometry, for fast and ultra-sensitive detection of multiple biomarkers (i.e. Matrix metalloproteinase-9 (MMP-9), Lipocalin-1 (LCN-1), Lactoferrin (LTF)) in tears for the diagnosis and classification of DED. This centimeter-scale concentric nanophotonic metasurface, which consists of millions of unique metallic nanostructures, was fabricated through a cost-effective nanoimprint lithography (NIL) process. The immune detection system based on the antibody-modified metasurface shows favorable detection selectivity, an ultra-high sensitivity (3350 pixels/Refractive Index Unit (RIU)) and low limit of detection (LOD) (0.3 ng/mL for MMP-9, 1 ng/mL for LTF, and 0.5 ng/mL for LCN-1). Further clinical sampling and detection results demonstrated that this multi-biomarker detection system enabled accurate determination and symptom classification of DED, manifesting high correlation and consistency with clinical diagnosis results. The advantages such as low sample consumption, one-step detection, simple operation, and simultaneous detection of multiple biomarkers make the platform promising for screening and detecting a broader range of biomarker combinations in clinical practice.

Association of ocular surface and meibomian gland alterations with silicone hydrogel contact lens wear.

PURPOSE: To evaluate silicone hydrogel contact lens (SH-CL) effects on the meibomian glands, corneal structure, and ocular surface parameters. METHODS: Fifty SH-CL wearers for at least 6 months, and 50 sex and age-matched control subjects were recruited for this cross-sectional study. Visual display terminal (VDT) work and CL wear duration were questioned, ocular surface and tear functions were evaluated using OSDI questionnaire, tear break-up time (TBUT), corneal fluorescein staining, and Schirmer test. Corneal sensitivity was measured with Cochet-Bonnet aesthesiometry. Meibography and in vivo confocal microscopy (IVCM) were performed to evaluate meibomian glands and corneal structure. Intergroup comparisons were made using the Chi-square test, Wilcoxon test, or Kruskal-Wallis test. RESULTS: In the CL group, TBUT was shorter (P = 0.01), corneal fluorescein staining (P = 0.04), OSDI scores (P < 0.001), and meiboscores (P < 0.001) were higher than the control group. The biomicroscopic evaluation revealed meibomian gland dysfunction (MGD) in 34 % of the CL group and 20 % of the control group, which was not statistically significant (P > 0.05). IVCM showed that endothelial cell density was lower (P = 0.01) and polymegethism was higher (P < 0.001) in the CL group. Subbasal nerve density and corneal sensitivity measurements were similar in the two groups (P > 0.05). The longer VDT work duration was associated with increased CFS in the CL group (P = 0.05). CONCLUSION: The results showed that SH-CL wear increased dry eye symptoms and ocular discomfort, especially in longer VDT work duration. Meibography revealed significantly worse results in SH-CL wearers. SH-CL-related ocular discomfort seems to be more associated with MGD rather than neurosensorial alterations.

A chemical signal in human female tears lowers aggression in males.

Rodent tears contain social chemosignals with diverse effects, including blocking male aggression. Human tears also contain a chemosignal that lowers male testosterone, but its behavioral significance was unclear. Because reduced testosterone is associated with reduced aggression, we tested the hypothesis that human tears act like rodent tears to block male aggression. Using a standard behavioral paradigm, we found that sniffing emotional tears with no odor percept reduced human male aggression by 43.7%. To probe the peripheral brain substrates of this effect, we applied tears to 62 human olfactory receptors in vitro. We identified 4 receptors that responded in a dose-dependent manner to this stimulus. Finally, to probe the central brain substrates of this effect, we repeated the experiment concurrent with functional brain imaging. We found that sniffing tears increased functional connectivity between the neural substrates of olfaction and aggression, reducing overall levels of neural activity in the latter. Taken together, our results imply that like in rodents, a human tear-bound chemosignal lowers male aggression, a mechanism that likely relies on the structural and functional overlap in the brain substrates of olfaction and aggression. We suggest that tears are a mammalian-wide mechanism that provides a chemical blanket protecting against aggression.

Detection of pro-inflammatory cytokines in healthy canine tears using Canine Cytokine SpikeMix™ mass spectrometry via multiple reaction monitoring.

PURPOSE: To evaluate the efficacy of the Canine Cytokine SpikeMix™ and MRM-MS for detecting pro-inflammatory cytokines in canine tears from healthy research Beagles. METHODS: A complete ophthalmic examination was performed on 15 healthy research Beagles to verify no ophthalmic diseases. Tears were collected OU by placing a Weck-Cel® cellulose spear in the ventral conjunctival fornix for 1 min. The Weck-Cel® spear was placed in a 2.0 mL tube with a centrifuge filter forcing tears to flow through the filter into the bottom of the tube. The tears were analyzed using the Canine Cytokine SpikeMix™ and MRM-MS. Descriptive data from this study was reported as the normalized total peak area (nTPA) and median (range) using data imported from the online MRM-MS Skyline program. RESULTS: The level of 16 pro-inflammatory cytokines was successfully detected in all 15 dogs. The four cytokines with the highest median amounts in the samples were IL-2 = 0.1243 (0.019-6.7289), IL-6 = 0.964 (0.0036-16.9365), TNFα = 0.1644 (0.0096-0.7138), and CSF-2 = 0.4022 (0.1475-2.6208). CONCLUSIONS: This study revealed that 16 pro-inflammatory cytokines in canine tears from healthy dogs can be detected with Canine Cytokine SpikeMix™ and MRM-MS.

Elucidating the Molecular Interactions between Lipids and Lysozyme: Evaporation Resistance and Bacterial Barriers for Dry Eye Disease.

Dry eye disease (DED) is a chronic condition characterized by ocular dryness and inflammation. The tear film lipid layer (TFLL) is the outermost layer composed of lipids and proteins that protect the ocular surface. However, environmental contaminants can disrupt its structure, potentially leading to DED. Although the importance of tear proteins in the TFLL functionality has been clinically recognized, the molecular mechanisms underlying TFLL-protein interactions remain unclear. In this study, we investigated tear protein-lipid interactions and analyzed their role in the TFLL functionality. The results show that lysozyme (LYZ) increases the stability of the TFLL by reducing its surface tension and increasing its surface pressure, resulting in increased TFLL evaporation and bacterial invasion resistance, with improved wettability and lubrication performance. These findings highlight the critical role of LYZ in maintaining ocular health and provide potential avenues for investigating novel approaches to DED treatment and patient well-being.

Comparative Biophysical Study of Meibomian Lipids of Wild Type and Soat1-Null Mice: Implications to Meibomian Gland Dysfunction and Dry Eye Disease.

Purpose: The biophysical roles of Meibomian lipids (MLs) played in health and meibomian gland dysfunction (MGD) are still unclear. The purpose of this research is to establish the composition-structure-functional correlations of the ML film (MLF) using Soat1-null mice and comprehensive in vitro biophysical simulations. Methods: MLs were extracted from tarsal plates of wild type (WT) and Soat1 knockout (KO) mice. The chemical composition of ML samples was characterized using liquid chromatography - mass spectrometry. Comprehensive biophysical studies of the MLFs, including their dynamic surface activity, interfacial rheology, evaporation resistance, and ultrastructure and topography, were performed with a novel experimental methodology called the constrained drop surfactometry. Results: Soat1 inactivation caused multiple alternations in the ML profile. Compared to their WT siblings, the MLs of KO mice were completely devoid of cholesteryl esters (CEs) longer than C18 to C20, but contained 7 times more free cholesterol (Chl). Biophysical assays consistently suggested that the KO-MLF became stiffer than that of WT mice, revealed by reduced film compressibility, increased elastic modulus, and decreased loss tangent, thus causing more energy loss per blinking cycle of the MLF. Moreover, the KO mice showed thinning of their MLF, and reduced evaporation resistance. Conclusions: These findings delineated the composition-structure-functional correlations of the MLF and suggested a potential biophysical function of long-chain CEs in optimizing the surface activity, interfacial rheology, and evaporation resistance of the MLF. This study may provide novel implications to pathophysiological and translational understanding of MGD and dry eye disease.

Ocular Surface Evaluation in Immunoglobulin G4-Related Ophthalmic Disease.

PURPOSE: To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. DESIGN: Cross-sectional, matched case-control comparison study. METHODS: This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings. RESULTS: A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P = .0187), lid margin telangiectasia (P = .0360), lid-parallel conjunctival folds (P = .0112), papillae (P = .0393), meibomian gland plugging (P = .0001), meibomian gland expressibility (P = .0001), and meibum quality (P = .0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P = .001 and .0003), and tear meniscus height (P = .0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P = .0166) and Schirmer test results (P = .0243) were lower in IgG4-ROD patients. Upper (r = 0.336, P = .0140) meibomian gland dropouts and NITBUT (r = -0.293, P = .0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r = -0.341, P = .0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001). CONCLUSIONS: IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.

Effects on the Human Tear Film of Applying Skin Lipids to the Ocular Surface.

PURPOSE: The effect of skin lipids on the formation and stability of the human tear film was investigated. METHODS: Skin swab substances (SSSs) were applied to the eyes of volunteers and studied using fluorescein or with TearView, which records infrared emissivity showing tear film integrity in real time. Results were compared with similar experiments using castor oil, freshly collected meibum, or acetic acid, which simulated the low pH of the skin. RESULTS: Fluorescein and TearView results were comparable. TearView showed the natural unaltered tear film over the whole eye, instant changes to the tear film, and meibomian gland activity. Minimal amounts of SSS destroyed the integrity of the film and caused pain. Corneal epithelial damage could be detected. TearView showed that SSS stimulated meibomian gland secretion if applied directly to the posterior eyelid margin. Excess meibum had no effect on the tear film spread or integrity. Castor oil formed floating lenses on the tear film which were spread by a blink but then condensed back toward themselves. There was no pain or surface damage with these oils. CONCLUSIONS: SSS contamination of the ocular surface disrupts the tear film, causes stinging, and fluorescein staining of the corneal epithelial cells after a blink. SSS stimulates meibomian gland activity. It is possible that various ocular conditions associated with dry eye, such as blepharitis and ocular rosacea, may compromise a meibomian lipid barrier of the eye lid margin. Skin lipids would then have access to the ocular surface and cause dry eye symptoms.

Effects of elevated serum estrogen on dry eye in women undergoing in vitro fertilisation.

PURPOSE: Sex hormones impact inflammatory and immune-mediated diseases. During IVF (in vitro fertilisation) treatment, circulating estrogen levels increase dramatically (10-50x) alongside changes in other hormones. This study examined changes in dry eye with IVF and its relationship with sex hormones. METHODS: A two visit study was conducted on first day of menstruation when estrogen levels are lowest (baseline visit), and on day 9-11 (peak estrogen visit (PO)) of IVF. Symptoms of dry eye and ocular pain and signs of dry eye were examined. Serum hormone levels were assessed using mass spectrometry and immunoassay. Changes in signs and symptoms and associations were explored. Hierarchical multiple regression analysis assessed factors contributing to signs and symptoms. RESULTS: 40 women (36.2 ± 4.0 years) completed the study. Baseline and PO oestradiol (E2) levels were 28.9 pg/ml (20) (median (IQR)); 1360 pg/ml (1276) respectively. Ocular pain and dry eye symptoms worsened (p = 0.02 and p < 0.01) and tear break up and tear secretion values decreased (p = 0.005 and 0.01) at PO. Higher E2 and lower luteinizing hormone (LH) were associated with worsening of dry eye symptoms (ρ = 0.34 p = 0.03, ρ = -0.49 p = 0.001). Reduction in LH and increase in progesterone (P4) were associated with increased ocular pain (ρ = 0.45, p = 0.004 and ρ = 0.39, p = 0.01). Dry eye symptoms were predicted by LH and tear break up (p = 0.02; R2 = 0.18). CONCLUSIONS: IVF treatment resulted in significantly increased ocular symptoms and tear film alterations although these changes were not clinically significant. Dry eye signs and symptoms were poorly predicted by hormone levels.

Relationship Between Human Meibum Lipid Composition and the Severity of Meibomian Gland Dysfunction: A Spectroscopic Analysis.

Purpose: Information on the relationship between meibum lipid composition and severity of meibomian gland dysfunction (MGD) is limited. The purpose of this study was to analyze the molecular components of meibum collected from individuals with no MGD, mild-to-moderate MGD, and severe MGD. Methods: Adults with and without MGD were enrolled in a prospective, multicenter, exploratory clinical trial (ClinicalTrials.gov Identifier: NCT01979887). Molar ratios of cholesteryl ester to wax ester (RCE/WE) and aldehyde to wax ester (Rald/WE) in meibum samples were measured with 1H-NMR spectroscopy. Results were evaluated for participants grouped by MGD disease status and severity (non-MGD, mild-to-moderate MGD, and severe MGD), as defined by maximum meibum quality scores, Schirmer test results, and Subject Ocular Symptom Questionnaire responses. Results: Sixty-nine meibum samples from 69 individuals were included in the analysis: 24 non-MGD, 24 mild-to-moderate MGD, and 21 severe MGD. Mean RCE/WE was 0.29 in non-MGD, 0.14 in mild-to-moderate MGD (P = 0.038 vs. non-MGD, 51% lower), and 0.07 in severe MGD (P = 0.16 vs. mild-to-moderate MGD, 52% lower; P = 0.002 vs. non-MGD, 76% lower). Mean Rald/WE was 0.00022 in non-MGD, 0.00083 in mild-to-moderate MGD (P = 0.07 vs. non-MGD, 277% higher), and 0.0024 in severe MGD (P = 0.003 vs. mild-to-moderate MGD, 190% higher; P < 0.001 vs. non-MGD, 992% higher). Conclusions: RCE/WE was lowest and Rald/WE was highest in the severe MGD cohort, suggesting that these meibum constituent molar ratios may result from the pathophysiology associated with MGD and can impact ocular surface lipid and tear film homeostasis. These findings may potentially help identify targets for MGD treatment.

MicroRNA Profiling from Tears as a Potential Non-invasive Method for Early Detection of Diabetic Retinopathy.

Diabetic retinopathy (DR) is a vascular complication of diabetes that can lead to partial or complete loss of vision. Early detection and treatment of DR can prevent blindness. Regular clinical examination is recommended for DR diagnosis; however, it is not always possible or feasible due to limited resources, expertise, time, and infrastructure. Several clinical and molecular biomarkers are proposed for the prediction of DR including microRNAs. MicroRNAs are a class of small non-coding RNAs that are found in biofluids and can be measured using reliable and sensitive methods. The most commonly used biofluid for microRNA profiling is plasma or serum; however, tear fluid (tears) is also demonstrated to contain microRNAs. MicroRNAs isolated from tears present a non-invasive source for DR detection. Different methods of microRNA profiling are available including digital PCR-based methods that can detect up to a single copy of microRNA in the biofluids. Here, we describe microRNA isolation from tears using manual method as well as using a high-throughput automated platform followed by microRNA profiling using digital PCR system.

Experimental Analysis of Tear Fluid and Its Processing for the Diagnosis of Multiple Sclerosis.

A pilot analysis of the tear fluid of patients with multiple sclerosis (MS) collected by glass microcapillary was performed using various experimental methods: liquid chromatography-mass spectrometry, Raman spectroscopy, infrared spectroscopy, and atomic-force microscopy. Infrared spectroscopy found no significant difference between the tear fluid of MS patients and the control spectra; all three significant peaks were located at around the same positions. Raman analysis showed differences between the spectra of the tear fluid of MS patients and the spectra of healthy subjects, which indicated a decrease in tryptophan and phenylalanine content and changes in the relative contributions of the secondary structures of the polypeptide chains of tear proteins. Atomic-force microscopy exhibited a surface fern-shaped dendrite morphology of the tear fluid of patients with MS, with less roughness on both oriented silicon (100) and glass substrates compared to the tear fluid of control subjects. The results of liquid chromatography-mass spectrometry showed downregulation of glycosphingolipid metabolism, sphingolipid metabolism, and lipid metabolism. Proteomic analysis identified upregulated proteins in the tear fluid of patients with MS such as cystatine, phospholipid transfer protein, transcobalamin-1, immunoglobulin lambda variable 1-47, lactoperoxidase, and ferroptosis suppressor protein 1; and downregulated proteins such as haptoglobin, prosaposin, cytoskeletal keratin type I pre-mRNA-processing factor 17, neutrophil gelatinase-associated lipocalin, and phospholipase A2. This study showed that the tear proteome in patients with MS is modified and can reflect inflammation. Tear fluid is not a commonly used biological material in clinico-biochemical laboratories. Experimental proteomics has the potential to become a promising contemporary tool for personalized medicine, and it might be applied in clinical practice by providing a detailed analysis of the tear-fluid proteomic profile of patients with MS.

Changes caused by fluorescein in the tear film evaluated with hybrid break-up time test as a new method - Part Two: Its effect on breakup locations and other quantitative values.

OBJECTIVES: To examine the changes caused by fluorescein in the tear film by analyzing the qualitative parameters such as breakup location and also detailed quantitative parameters. METHODS: After determining the break-up time (BUT) value and breakup locations by the Non-invasive break-up time (NI-BUT) method, we re-evaluated the changes in the tear film stained with fluorescein using the topographical method. We called the topographic evaluation of the tear film stained with fluorescein as the Hybrid-BUT test. The results for the parameters obtained for each participant by the NI-BUT and Hybrid-BUT tests were compared. RESULTS: Our study was conducted with 82 participants aged between 18 and 58 years (mean age 34.1 ± 11.1). The mean first break-up time value (BUT1) was 4.1 ± 2.7 s on the NI-BUT test versus 5.1 ± 3.2 s on the Hybrid-BUT test (p = 0.029). The mean average of all break-up time values (BUTAvg) for each participant was 7.2 ± 3.2 s on the NI-BUT test versus 8.4 ± 3.1 s on the Hybrid-BUT test (p = 0.004). After dividing the corneal surface into quadrants of 90°, there was no significant difference in the comparison of the locations of the first breakup (QUAD(First breakup)), the second breakup (QUAD(2nd breakup)) and the third breakup (QUAD(3rd breakup)) between the two tests (p>0.05). CONCLUSIONS: Fluorescein affects quantitative values rather than qualitative parameters in tear film. We observed that the change caused by fluorescein in tear film break-up time could be detected objectively and in a documented manner using Hybrid-BUT test.

Effects of physical activity/exercise on tear film characteristics and dry eye associated symptoms: A literature review.

PURPOSE: To conduct a review of the literature in order to identify the potential association between physical activity or exercise and the objective signs and/or subjective symptoms of dry-eye disease. METHODS: A review of PubMed and Web of Science databases was performed, according to the PRISMA guidelines. The papers included in the review addressed the relationship of physical activity or exercise with dry-eye associated signs (changes in tear volume, osmolarity or biochemical composition) and/or subjective symptoms. RESULTS: A total of 16 papers were included. In eight, the changes in tear film volume, osmolarity and/or biochemical composition were studied after a single, acute bout of aerobic exercise. In another eight, changes in dry-eye associated symptoms were studied in relation to the habitual practice of physical activity or to prescribed exercise programmes. Acute responses of the tear film to exercise included: a) an increase of tear volume, without an increase of the tear break-up time; b) a trend to increase tear osmolarity, although within its physiological range; and c) a reduced concentration of several cytokines, and other molecular markers of inflammation or oxidative stress. Long-term exposure to physical activity or exercise programmes was associated with relief of dry-eye associated symptoms and a trend to increased tear break-up time. CONCLUSIONS: Despite a high heterogeneity in the studied population, study designs and methods, the current body of evidence suggests a potential role for physical activity as a modulatory stimulus for the proper functioning of the tear film and/or the relief of dry-eye symptoms.

Meibomian Gland Dysfunction in Primary Acquired Nasolacrimal Duct Obstruction.

This study was designed to investigate the influence of primary nasolacrimal duct obstruction (PANDO) on the structure and function of the Meibomian gland and to examine whether it is related to functional failure after dacryocystorhinostomy surgery. Medical records of patients diagnosed as PANDO from August 2021 to February 2022 were retrospectively studied. Results of slit lamp examination, lacrimal drainage test, tear break-up time, anterior segment optical coherence tomography, and meibography were collected. Tear meniscus height, tear break-up time, meiboscore, and lipid layer thickness of tear membrane were parameters compared between the eyes with complete PANDO and the control group. Medical records of 44 patients, therefore 88 eyes were collected, and there were 28 eyes with complete PANDO (total obstruction group), while normal eyes (control group) were 30. Mean tear meniscus height was significantly higher than that of the control group ( P value<0.001), but tear break-up time ( P value=0.322), lipid layer thickness ( P value=0.755), and meiboscore ( P value=0.268) were not significantly different. However, in the cases with moderate and severe meibomian gland destruction, the lipid layer thickness of the total obstruction group was significantly thinner than the control group. Lipid secretion of meibomian glands was less in eyes with PANDO than in eyes without PANDO, under moderate to severe meibomian gland destruction. It can lead to persistent epiphora after dacryocystorhinostomy due to a compensatory response against evaporative dry eye disease. Patients should be educated before the decision to undergo surgeries about the possibilities of persistent epiphora. Further studies are needed to prove the mechanism of meibomian gland function disturbance in PANDO.