[Changes in the precorneal tear film at various stages of keratoconus]. / Izmenenie prekorneal'noi sleznoi plenki pri razlichnykh stadiyakh keratokonusa.

The combination of keratoconus (KC) with signs of dry eye disease (DES) has been described in numerous scientific publications. At the same time, there is a relationship between KC stage and an increase in the severity of DES symptoms, however, there is still no common understanding of the severity of xerotic process depending on the clinical course of keratectasia. PURPOSE: This study assesses the changes in the state of the precorneal tear film in KC relative to the stages of the disease. MATERIAL AND METHODS: The study included 50 patients (100 eyes) with bilateral non-operated KC from subclinical to stage IV. The following methods were used for a comprehensive assessment of the condition of the tear film: biomicroscopy of the anterior segment of the eye using vital dyes, functional tests (Norn, Schirmer, Jones tests), tearscopy of the lipid layer of the tear film with software processing of the results, OCT-meniscometry, as well as filling out the OSDI questionnaire by patients. RESULTS: The following significant changes were revealed as the KC stage progressed: an increase in the area of staining of the ocular surface with vital dyes, a decrease in the results of the Norn functional test and OCT-meniscometry, an increase in the areas of smaller thickness of lipids and areas of their complete absence according to tearscopy, as well as an increase in scores of the OSDI questionnaire. CONCLUSION: A comprehensive assessment of the condition of the tear film in KC indicates the relationship and the strengthening of the signs of DES as keratectasia progresses, and can be considered as justification for the need to prescribe tear replacement and reparative therapy that improves the condition of the ocular surface and stabilizes the precorneal tear film.

Multifunctional Cerium Oxide Nanozyme for Synergistic Dry Eye Disease Therapy.

Dry eye disease (DED) is a chronic multifactorial ocular surface disease mainly caused by the instability of tear film, characterized by a series of ocular discomforts and even visual disorders. Oxidative stress has been recognized as an upstream factor in DED development. Diquafosol sodium (DQS) is an agonist of the P2Y2 receptor to restore the integrity/stability of the tear film. With the ability to alternate between Ce3+ and Ce4+, cerium oxide nanozymes could scavenge overexpressed reactive oxygen species (ROS). Hence, a DQS-loaded cerium oxide nanozyme was designed to boost the synergistic treatment of DED. Cerium oxide with branched polyethylenimine-graft-poly(ethylene glycol) as nucleating agent and dispersant was fabricated followed with DQS immobilization via a dynamic phenylborate ester bond, obtaining the DQS-loaded cerium oxide nanozyme (defined as Ce@PBD). Because of the ability to mimic the cascade processes of superoxide dismutase and catalase, Ce@PBD could scavenge excessive accumulated ROS, showing strong antioxidant and anti-inflammatory properties. Meanwhile, the P2Y2 receptors in the conjunctival cells could be stimulated by DQS in Ce@PBD, which can relieve the incompleteness and instability of the tear film. The animal experiments demonstrated that Ce@PBD significantly restored the defect of the corneal epithelium and increased the number of goblet cells, with the promotion of tear secretion, which was the best among commercial DQS ophthalmic solutions.

The Effect of Conjunctiva-Müller Muscle Resection on Tear Oxidative Stress Levels in Patients with Blepharoptosis

Objectives: To examine changes in tear oxidative stress levels and tear film functions in patients with blepharoptosis and dermatochalasis following conjunctiva-Müller muscle resection (CMMR) and blepharoplasty surgeries. Materials and Methods: This prospective study included 32 healthy controls and 62 patients with blepharoptosis or dermatochalasis. CMMR surgery was performed in 20 eyes and upper blepharoplasty was performed in 42 eyes. Tear oxidative stress markers (8-hydroxy-2'-deoxyguanosine [8-OHdG] and 4-hydroxy-2-nonenal [4-HNE]) were quantified by enzyme-linked immunosorbent assay and tear film functions were evaluated preoperatively and at 1 and 6 months postoperatively. The same assessments were performed in the control group at the same time points. Results: Preoperative tear 8-OHdG and 4-HNE levels were lower in healthy controls (52.8±13.5 ng/mL and 27.8±6.4 ng/mL, respectively) compared to patients with dermatochalasis (86.1±37.2 ng/mL and 29.8±11.1 ng/mL, respectively) and blepharoptosis (90.4±39.3 ng/mL and 43.1±4.2 ng/mL, respectively) (p<0.001). 8-OHdG levels were increased at 1 month after CMMR, while both markers were decreased 1 month postoperatively in the blepharoplasty group (p=0.034). Schirmer 1 and OSDI scores did not change throughout the visits in both patient groups, but a temporary decrease in tear break-up time (TBUT) was observed after CMMR (p=0.017). Conclusion: Dermatochalasis and blepharoptosis were associated with higher tear oxidative stress levels. CMMR surgery caused a temporary decrease in TBUT scores and an increase in oxidative stress in the first postoperative month.

Management of Dry Eye Disease for Intraocular Lens Power Calculation in Cataract Surgery: A Systematic Review.

Cataracts are characterized by the crystalline lens of the eye becoming cloudy, and dry eye disease (DED) is a multifactorial disease in which the homeostasis of the tear film is lost. As the prevalence of both diseases increases with age, there is a high prevalence of DED among patients who are candidates for cataract surgery. In recent years, cataract surgery has evolved from vision restoration surgery to refractive surgery. To achieve good surgical outcomes, it is necessary to minimize postoperative refractive error in intraocular lens (IOL) power calculation, which requires accurate preoperative keratometry measurements. A stable tear film is important for the accuracy and reproducibility of keratometry measurements, and DED may have a deleterious effect. In this study, original articles that focused primarily on findings related to this topic were evaluated. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Although appropriate DED diagnoses were not presented in the articles evaluated in this review, it was confirmed that the clinical signs of DED, particularly the shortening of the tear film break-up time (TBUT), negatively impact IOL power calculations. Improvement in these clinical signs might mitigate the negative effects on these calculations.

The influence of the tear film on the intraocular pressure and the corneal biomechanical properties analyzed with the Ocular Response Analyzer / La influencia de la película lagrimal sobre la presión intraocular y las propiedades biomecánicas corneales analizadas con el Analizador de Respuesta Ocular

Purpose: As ocular dryness and glaucoma are more prevalent with increasing age, understanding how the tear film affects tonometry is important. The present study aims to understand the impact that changes in the tear film have on intraocular pressure (IOP), corneal hysteresis, and corneal resistance factor measurements. Methods: Cross-sectional research was conducted and 37 patients were assessed. The tear film lipid layer and the non-invasive break-up time (NIBUT) were evaluated using the Tearscope Plus (Keeler, Windsor, UK). Dry eye symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. IOP was measured using rebound tonometry and the Ocular Response Analyzer (ORA, Reichert). Corneal biomechanical properties were measured using ORA. Results: It was found that an increase in the IOP measured with the iCare was directly correlated with the subclass that evaluated symptomatology associated with environmental factors (r = 0.414, p<0.05, Spearman). Goldmann-correlated IOP (IOPg) and Corneal-compensated IOP (IOPcc) values were statistically significantly different between the various interferometric patterns (p<0.05). It was also found that an increase in the corneal biomechanical properties measured with ORA was directly correlated with the overall scores obtained when using the OSDI and some of its subclasses. Conclusions: Tear film interferometric patterns were shown to have some impact on the IOP measured using ORA. The IOP measured with iCare seems to be related to the symptomatology obtained from OSDI. Corneal biomechanical properties were related to the OSDI total score and some of its subclasses. An increase in symptomatology was associated with an increase in the measured biomechanical properties of the cornea.(AU)

Ocular surface changes in moderate-to-severe acne vulgaris.

AIM: To investigate ocular surface disorders and tear function changes in patients with acne vulgaris and explore the potential relationship between acne vulgaris and dry eye. METHODS: This cross-sectional study included right eyes of 53 patients with acne vulgaris and 54 healthy controls. The participants completed the Ocular Surface Disease Index (OSDI) questionnaire. The following ocular surface-related parameters were measured: tear meniscus height (TMH), noninvasive tear breakup time (NIBUT), Schirmer I test (SIT), lipid layer thickness (LLT) score of the tear film, meibum score, meibomian gland orifice obstruction score, the ratio of meibomian gland loss, conjunctival hyperemia score, and corneal fluorescein staining (CFS) score. RESULTS: The stability of the tear film decreased in acne vulgaris patients. In the acne group, the TMH and NIBUT were lower, whereas the OSDI, meibum score, meibomian gland orifice obstruction score, ratio of meibomian gland loss, and conjunctival hyperemia score were higher compared with controls (P<0.05). There were no significant differences in the CFS score, SIT, or LLT score between the groups (P>0.05). In two dry eye groups, the TMH, NIBUT, and LLT score were lower in the acne with dry eye (acne-DE) group, and the meibum score, meibomian gland orifice obstruction score, ratio of meibomian gland loss and conjunctival hyperemia score in the acne-DE group were higher (P<0.05). There were no significant differences between OSDI, SIT, and CFS score (P>0.05). CONCLUSION: Patients with moderate-to-severe acne vulgaris are more likely to experience dry eye than those without acne vulgaris. Reduced tear film stability and meibomian gland structure dysfunction are more pronounced in patients with moderate-to-severe acne and dry eye.

Influence of midday removal and re-application of a scleral lens on fluid reservoir thickness, pre-lens tear film quality and visual acuity.

PURPOSE: To investigate whether the midday removal and re-application of scleral lenses (SL) influences fluid reservoir (FR) thickness, pre-lens tear film quality and visual acuity. METHODS: Two clinical experiments were conducted. A total of 49 keratoconic eyes were evaluated for Part1(tear film and visual acuity analysis) and 12 keratoconic eyes for Part2 (FR thickness analysis). All subjects were wearing 16.4 mm SL for more than 12-months. Tear Film Surface Quality (TFSQ) was evaluated with Medmont E300 at more than 120 min of SL wear, 10 min after SL removal (pre-corneal TFSQ) and 5 min after re-apply the same SL. High and Low Contrast Visual Acuity (HCVA and LCVA) were also assessed with the SL on eye (before and after re-application). For Part2, Anterior OCT (MOptim MOcean4000, China) measurements were taken with and without the SL (at the same time points of Part1) and three outcomes were evaluated: FR thickness, SL thickness (control measurement) and corneal thickness. RESULTS: Removing and re-applying a SL had a statistically significant positive impact on TFSQ, with an improvement from 0.26 ± 011 to 0.16 ± 0.08 (p = 0.001). This was accompanied by a statistically significant improvement in LogMAR HCVA (from 0.10 ± 0.09 to 0.08 ± 0.08, p < 0.001) and LCVA (from 0.39 ± 0.13 to 0.36 ± 0.13, p < 0.001). Regarding Part2 of the study, a statistically significant increase in FR thickness was observed after SL re-application (from 223.64 ± 48.08 µm to 267.81 ± 80.03 µm, p = 0.007). No changes in corneal thickness were observed. CONCLUSIONS: Midday removal and re-application of a scleral lens positively impacted pre-lens tear film surface quality, although the observed improvement in visual acuity does not constitute a clinically significant change. Clinicians should consider that removing and reapplying a scleral lens may result in an overestimation of the fluid reservoir thickness, which could affect clinical assessments and treatment decisions.

Intense Pulsed Light Therapy for Dry Eye Disease: Analyzing Temporal Changes in Tear Film Stability and Ocular Surface between IPL Sessions.

BACKGROUND: Dry eye disease (DED), a prevalent condition with a multifactorial etiology, significantly impacts global health by causing discomfort and visual disturbance. This historical cohort study evaluates the efficacy of Intense Pulsed Light (IPL) therapy on meibomian gland dysfunction (MGD)-related evaporative DED. METHODS: The study involved 110 patients (220 eyes) who underwent IPL therapy. Ethical approval was secured, and informed consent was obtained from all participants. A Tearcheck® (ESWvision, Houdan, France) device was used for ocular surface evaluation, measuring tear film stability (NIFBUT, NIABUT), tear film quantity (CTMH, TTMH), and inflammation (OSIE). The study assessed tear film and ocular surface health across multiple IPL sessions. RESULTS: Significant improvements were observed in subjective symptoms (EFT score increased from 29.10 ± 8.87 to 35.91 ± 7.03, p < 0.01), tear film stability (NIFBUT increased from 9.37 ± 6.04 to 10.78 ± 5.83 s, p < 0.01; NIABUT increased from 11.07 ± 4.98 to 12.34 ± 4.66 s, p < 0.01), and tear film surface evaluation (TFSE score decreased from 337.78 ± 414.08 to 206.02 ± 240.44, p < 0.01). Tear film quantity remained unchanged (CTMH and TTMH, p > 0.05). CONCLUSIONS: IPL therapy is a promising treatment for DED, improving symptoms and ocular surface health. Further research is warranted to explore long-term efficacy and optimization.

The Severity of Diabetic Retinopathy Corresponds with Corneal Nerve Alterations and Ocular Discomfort of the Patient.

Diabetic retinopathy (DR) remains the leading cause of blindness in the working-age population. Its progression causes gradual damage to corneal nerves, resulting in decreased corneal sensitivity (CS) and disruption of anterior-eye-surface homeostasis, which is clinically manifested by increased ocular discomfort and dry eye disease (DED). This study included 52 DR patients and 52 sex- and age-matched controls. Ocular Surface Disease Index (OSDI) survey, tear film-related parameters, CS, and in vivo corneal confocal microscopy (IVCM) of the subbasal plexus were performed. Furthermore, all patients underwent tear sampling for neurotrophin and cytokine analysis. OSDI scores were greater in DR patients than in controls (p = 0.00020). No differences in the Schirmer test score, noninvasive tear film-break-up time (NIBUT), tear meniscus or interferometry values, bulbar redness, severity of blepharitis or meibomian gland loss were found. In the DR group, both the CS (p < 0.001), and the scotopic pupil diameter (p = 0.00008) decreased. IVCM revealed reduced corneal nerve parameters in DR patients. The stage of DR was positively correlated with the OSDI (Rs = +0.51, 95% CI: + 0.35-+0.64, p < 0.001) and negatively correlated with IVCM corneal nerve parameters and scotopic pupillometry (Rs = -0.26, 95% CI: -0.44--0.06, p = 0.0097). We found negative correlations between the OSDI and IVCM corneal innervation parameters. The DR group showed lower tear film-brain-derived neurotrophic factor (BDNF) levels (p = 0.0001) and no differences in nerve growth factor (NGF)-ß, neurotrophin (NT)-4, vascular endothelial growth factor (VEGF), interleukin (IL)-1ß, IL-4, IL-5, IL-6, or IL-12 concentrations. Tumor necrosis factor (TNF)-α, IL-2, IL-8, IL-10, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon (IFN)-γ levels were decreased among patients with DR. Corneal innervation defects have a direct impact on patients' subjective feelings. The evolution of DR appears to be associated with corneal nerve alterations, emphasizing the importance of IVCM.

Dry Eye Disease: An Update on Changing Perspectives on Causes, Diagnosis, and Management.

Dry eye disease is a common clinical problem encountered by ophthalmologists worldwide. Interest in this entity has increased in recent years due to the consequences it has on the ocular surface after any surface procedure. With changing times, several new factors have come to light that can influence this disease. The effect of the COVID-19 pandemic has also been greatly felt, with a range of causes, starting from increased screen work to inflammatory processes, exacerbating the condition in many. With changes in the concepts of the etiopathogenesis of the disease, a paradigm shift has taken place in the approaches to treatment. More researchers are in favor of a new tear film-oriented approach that tries to localize the disease to a single component in the tear film. Innovation of newer techniques for the treatment of meibomian gland disease has also made its foray into clinical ophthalmology. Newer drug formulations and molecules are underway to better treat the inflammatory component of the disease. Many other receptors and targets for the treatment of dry eyes are being researched. This review hopes to provide a succinct, narrative summary of the relevant research on dry eye disease to date to increase awareness about the nature and future course of this disease and its management.

Inflammation due to ocular surface homeostasis imbalance caused by pterygia: tear lymphotoxin-alpha study and a literature review.

OBJECTIVE: To estimate the pterygium ocular surface state, and compare with healthy eyes and dry eyes. To investigate the inflammation due to pterygia growth by tear Lymphotoxin-alpha (LT α) test. DESIGN: Prospective, single-center study. PARTICIPANTS: 400 patients, divided into 100 pterygium group, 100 mild dry eye group, 100 moderate dry eye group, and 100 age-and sex-matched normal controls. METHODS: The non-invasive break-up time (NIBUT), tear meniscus height (TMH) test, corneal fluorescein staining (CFS), meibomian gland loss score (MGs), and lipid layer thickness (LLT) were evaluated in all patients. Pterygium status and ocular status in the pterygium group were collected. The tear LT α test was conducted in the pterygium patients group. RESULT: Pterygium can affect the ocular surface, leading to decreased tear film stability. The TMH, NIBUT, CFS, MGs, and lipid layer thickness can provide insights into this phenomenon. The presence of pterygium can change the structure and condition of the ocular surface. Tear LT α testing shows an abnormal decrease in LT α levels in pterygium patients. This indicates an immune-inflammation microenvironment that causes tissue repair deficiency. CONCLUSION: The dry eye triggered by the growth of pterygium may originate from the tear film instability due to pterygia. As an inflammatory index, LT α in the development of pterygium and the aggravation of dry eye patients can indicate that the ocular surface is in different inflammatory states. Future tear testing in LT α may be a potential indicator to assess the inflammatory status of the dry eye.

Repeatability of Noninvasive Break-Up Time Measurements using Keratograph Oculus 3.

AIM: The primary aim of this study is to evaluate the repeatability of noninvasive break-up time (NIBUT) measurement by keratograph when it is determined from one, two or three partial measurements, and to recommend a suitable methodology for practice. Another goal is to verify that repeated measurements do not affect the measured value. MATERIAL AND METHODS: Thirty-eight healthy volunteers (30 women and 8 men) aged between 19 and 50 years old were included in the study, in which only one eye of each volunteer was measured. The study was designed as a prospective one. Each subject adapted to the local conditions of the laboratory for 15 minutes and subsequently underwent two series of NIBUT measurements (test, retest) on an OCULUS 3 Keratograph. The minimum time interval between the two series was 10 minutes, in which each series contained three partial measurements approximately 3 three measurements in the given series. Repeatability was assessed by a Bland-Altman analysis and expressed as a repeatability coefficient. In every case, only the time of the first break-up of the tear film was monitored. RESULTS: The statistical analysis did not show statistically significant differences both between partial measurements of NIBUT in the individual series (p = 0.92, p = 0.81) and when comparing all six measurements (p = 0.95). The mean values of the partial measurements ranged from 13.6 s to 14.4 s. The repeatability coefficients were found to be 15.0 s, 12.1 s and 10.0 s for methodologies A, B and C, respectively. A supplementary analysis for 12 eyes with low NIBUT (< 10 s) showed statistically significantly better repeatability in this group, with coefficients of 7.0 s (methodology A), 6.0 s (B) and 4.6 s (C). CONCLUSION: Determination of NIBUT from three consecutive measurements (with a sufficient interval of ideally a few minutes) significantly improves repeatability. Such repeated NIBUT measurements do not have a significant effect on the measured value. The mentioned methodology for measuring NIBUT on a keratograph can be recommended for use in practice.

Peculiarities of local immunity in dry eye disease on the background of hormonal dysfunction.

OBJECTIVE: Aim: to determine the state of local immunity in DED on the background of hormonal dysfunction. PATIENTS AND METHODS: Materials and Methods: Of 32 women, 17 patients with diagnosed SM and 15 women of the control group were examined. The Ocular Surface Disease Index and the state of local immunity were defined by determining Ig As in lacrimal fluid (LF) by radial immunodiffusion in Mancini agar. RESULTS: Results: During the OSDI questionnaire, a mild degree of DED was detected in 21 (65.6%) women, and an average degree was observed in 11 (34.4%) patients with SM. On average, OSDI was 34.54 ±2.01. As a result of studies of the state of local immunity in patients with SM, a tendency to increase Ig As was noted, compared with the control group. An increase in Ig As in the lacrimal fluid in patients with SM to 0.34 ±0.09 g/l was found, compared with the control group (0.24 ±0.03 g/l). CONCLUSION: Conclusions: Using the OSDI questionnaire, the presence of DED was detected in women with SM, mainly mild and moderate degree. The obtained results of the state of local immunity indicate in favor of a nonspecific inflammatory process, accompanied by a decrease in local immune protection and leading to further changes in the ocular surface.

Prevalence of dry eye syndrome in a South African diabetic paediatric population.

BACKGROUND: Diabetes mellitus (DM) can be defined as a metabolic disorder that results from either the inability of insulin to perform its normal functions or decreased insulin secretion. Dry eye disease is a complex ailment of the tear film resulting in discomfort characterised by pain, a feeling of heavy eyes, grittiness, burning, dryness, itchiness, foreign body sensation, and visual disturbances. Patients with chronic conditions, i.e. DM, are more susceptible to developing dry eye due to various complications that may arise, such as, peripheral neuropathy, inflammatory alterations and reduced lacrimal gland function. AIM: To identify the prevalence of dry eye syndrome in paediatric patients diagnosed with Diabetes Mellitus (Type 1/2). METHOD: 37 children with diabetes and 40 healthy, age group matched controls were enrolled in this study. Participants underwent a complete dry eye assessment in the following order: Ocular Surface Disease Index (OSDI) and McMonnies questionnaire, meibomian gland evaluation using white light, Tear Break-up Test (TBUT), Phenol Red Thread (PRT) test and Tear film Osmolarity test. Duration of diabetes was used as the parameter. RESULTS: The incidence of dry eye syndrome was found to be higher among diabetics, with 15 (40.5 %) from the diabetic population compared to 4 (10.0 %) from the control group. TBUT and PRT test values were significantly reduced in children with diabetes (p < 0.001). TFO values were higher in the diabetics. No statistically significant differences were found the questionnaire scores, of the two groups, however the diabetic group appeared to be less symptomatic. CONCLUSION: Dry eye is more common in the diabetic paediatric population. TBUT and PRT results were found to be lower in diabetics. Results showed a strong correlation between duration of diabetes and TBUT values. Healthcare practitioners, working with children diagnosed with diabetes, should raise awareness as well as encourage early dry eye screening and intervention. CLINICAL SIGNIFICANCE: Due to the steady increase in the number of children and adolescents with diabetes, the characteristics and prevalence of dry eye syndrome in this population has become more valuable.

Tear film hTERT and corneal nerve characteristics in dry eye disease.

CLINICAL RELEVANCE: The behaviour of human telomerase reverse transcriptase (hTERT) in tears reflects its role in maintaining the ocular surface homoeostasis, as it is increased after the initial fitting of contact lenses and post-overnight lid closure. BACKGROUND: hTERT has been shown to respond to cellular stress in neurodegenerative diseases and to enhance axonal regeneration after peripheral axotomy in an animal model. This work investigated whether the behaviour of hTERT in the tear film reflects ocular surface inflammation and neuronal changes in the presence of dry eye disease. METHODS: Flush tears were collected from 18 participants with dry eye disease (14 females, 4 males, mean age 34.7 ± 5.2 years) and from 18 healthy participants without dry eye disease (8 females, 10 males, mean age 31.9 ± 5.8 years). Dry eye disease status was defined using the TFOS DEWS II diagnostic criteria. hTERT levels in tears were measured using enzyme-linked immunosorbent assays. Confocal images were taken at the level of the subbasal nerve plexus at the central cornea and at the inferior whorl, and the densities of corneal immune cells were evaluated as well as corneal nerve morphology metrics using a fully automated technique (University of Manchester, United Kingdom). RESULTS: In participants with dry eye disease, hTERT levels were significantly higher compared to controls (median [interquartile range]: 434 [320-600] ng/ml, and 184 [42-390] ng/ml, respectively, p = 0.01). Increased nerve fibre width at the inferior whorl, was seen in those with dry eyes (0.0219 [0.0214-0.0236] mm/mm compared to controls 0.0217 [0.0207 0.0222] p < 0.001), but no significant differences were found in the density of corneal immune cells. CONCLUSIONS: hTERT levels were elevated in participants with dry eye disease, and this was accompanied by increased nerve thickness in the inferior cornea. The hTERT response may reflect the stress induced to the ocular surface and corneal nerves due to having dry eye disease.

Tear biomarkers.

An extensive exploration of lacrimal fluid molecular biomarkers in understanding and diagnosing a spectrum of ocular and systemic diseases is presented. The chapter provides an overview of lacrimal fluid composition, elucidating the roles of proteins, lipids, metabolites, and nucleic acids within the tear film. Pooled versus single-tear analysis is discussed to underline the benefits and challenges associated with both approaches, offering insights into optimal strategies for tear sample analysis. Subsequently, an in-depth analysis of tear collection methods is presented, with a focus on Schirmer's test strips and microcapillary tubes methods. Alternative tear collection techniques are also explored, shedding light on their applicability and advantages. Variability factors, including age, sex, and diurnal fluctuations, are examined in the context of their impact on tear biomarker analysis. The main body of the chapter is dedicated to discussing specific biomarkers associated with ocular discomfort and a wide array of ocular diseases. From dry eye disease and thyroid-associated ophthalmopathy to keratoconus, age-related macular degeneration, diabetic retinopathy, and glaucoma, the intricate relationship between molecular biomarkers and these conditions is thoroughly dissected. Expanding beyond ocular pathologies, the chapter explores the applicability of tear biomarkers in diagnosing systemic diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and cancer. This broader perspective underscores the potential of lacrimal fluid analysis in offering non-invasive diagnostic tools for conditions with far-reaching implications.

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.

Automated tear film break-up time measurement for dry eye diagnosis using deep learning.

In the realm of ophthalmology, precise measurement of tear film break-up time (TBUT) plays a crucial role in diagnosing dry eye disease (DED). This study aims to introduce an automated approach utilizing artificial intelligence (AI) to mitigate subjectivity and enhance the reliability of TBUT measurement. We employed a dataset of 47 slit lamp videos for development, while a test dataset of 20 slit lamp videos was used for evaluating the proposed approach. The multistep approach for TBUT estimation involves the utilization of a Dual-Task Siamese Network for classifying video frames into tear film breakup or non-breakup categories. Subsequently, a postprocessing step incorporates a Gaussian filter to smooth the instant breakup/non-breakup predictions effectively. Applying a threshold to the smoothed predictions identifies the initiation of tear film breakup. Our proposed method demonstrates on the evaluation dataset a precise breakup/non-breakup classification of video frames, achieving an Area Under the Curve of 0.870. At the video level, we observed a strong Pearson correlation coefficient (r) of 0.81 between TBUT assessments conducted using our approach and the ground truth. These findings underscore the potential of AI-based approaches in quantifying TBUT, presenting a promising avenue for advancing diagnostic methodologies in ophthalmology.

Association between dryness sensation and ocular surface temperature and conjunctival blood flow in soft contact lens wearers.

PURPOSE: To investigate the association between dryness, ocular surface temperature (OST), and conjunctival blood flow (CBF) in soft contact lens (SCL) wearers after airflow stimulation. METHODS: After recruiting 21 SCL wearers (mean age, 25.3 ± 4.2 years), subjects used two different daily disposable silicone hydrogel SCLs (narafilcon A and delefilcon A lenses). On three of four measurement days, excluding the first, OST, CBF, tear meniscus height (TMH), and non-invasive tear break-up time (NIBUT) were measured after airflow stimulation at a rate of 3 m/s for 10 min. The measurements were conducted without SCLs on the first and second days, and with different SCLs on the third and fourth days. Dryness was evaluated using the visual analogue scale (VAS). These parameters were compared between the two types of SCLs, and their association with the dryness sensation was then investigated. RESULTS: Dryness was significantly weakly correlated with OST (r = -0.375, p < 0.05) and CBF (r = 0.339, p < 0.05). TMH, NIBUT, and VAS scores for dryness with the delefilcon A lens (0.15 ± 0.05 mm, 3.7 ± 01.7 s and 29.4 ± 16.9) were significantly higher, longer, and lower, respectively, than those with the narafilcon A lens (0.12 ± 0.05 mm, 2.3 ± 1.7 s and 35.9 ± 17.0; p < 0.05, p < 0.01 and p < 0.01). The changes in the OST and CBF between with and without the delefilcon A lens (-0.36 ± 0.35 °C and 0.99 ± 0.19) were significantly small compared to the narafilcon A lens (-0.60 ± 0.42 °C and 1.11 ± 0.21; p < 0.01 for both comparisons). CONCLUSION: Dryness was correlated with OST and CBF, which indicates that when dryness was high, OST was low and CBF was high. These results suggest that OST and CBF assessments are effective for evaluating dryness sensation.

Tear Film Dynamics in Visual Display Terminal Users: A Review of Impact on Goblet Cells, Lacrimal and Meibomian Gland Function.

PURPOSE: The prevalence of dry eye disease (DED) is rising among visual display terminal (VDT) users, a trend that correlates with the growing use of digital devices. The prevalence of VDT-associated DED is reported based on dry eye questionnaires; however, VDT's impact on tear film parameters is less understood. METHODS: A review of published literature on both the alterations in tear film observed in VDT users and the impact of various interventions on their tear film. RESULTS: Most studies show reduction in tear stability as well as reduction in the blink rate. The role of lacrimal gland hypofunction in visual display terminal (VDT) users is a subject of ongoing debate. Schirmer test values typically exceed the 10 mm threshold, suggesting normal tear production, and tear osmolarity remains within normal ranges but VDT users consistently present with lower Schirmer values compared to non-VDT users. The effects on Meibomian glands and mucin levels need more research as the numbers studied are small. Very few studies have analysed mucin levels in VDT users with reports of normal or reduced values. Even asymptomatic users can have tear film instability; hence, the diagnostic criteria need to be formulated and validated. Different interventions such as neurostimulation, blink improving apps, eyelid warming devices, moist goggles, and lubricants have been explored in VDT users but without a control arm and in asymptomatic VDT users in most studies. CONCLUSION: The alterations have been observed on aqueous, lipid and mucin components of the tear film, although the extent of the impact is variable across studies. There is urgent need of well-designed studies for studying the tear film changes and management options for the upcoming lifestyle epidemic in VDT users.