Duplex Tear Film Evaporation Analysis

Tear film thinning, hyperosmolarity, and breakup can cause irritation and damage to the human eye, and these form an area of active investigation for dry eye syndrome research. Recent research demonstrates that deficiencies in the lipid layer may cause locally increased evaporation, inducing conditions for breakup. In this paper, we explore the conditions for tear film breakup by considering a model for tear film dynamics with two mobile fluid layers, the aqueous and lipid layers. In addition, we include the effects of osmosis, evaporation as modified by the lipid, and the polar portion of the lipid layer. We solve the system numerically for reasonable parameter values and initial conditions and analyze how shifts in these cause changes to the system’s dynamics.     

Lipidomic analysis of epithelial corneal cells following hyperosmolarity and benzalkonium chloride exposure: New insights in dry eye disease

Dry eye disease (DED) is a multifactorial chronic inflammatory disease of the ocular surface characterized by tear film instability, hyperosmolarity, cell damage and inflammation. Hyperosmolarity is strongly established as the core mechanism of the DED. Benzalkonium chloride (BAK) - a quaternary ammonium salt commonly used in eye drops for its microbicidal properties - is well known to favor the onset of DED. Currently, little data are available regarding lipid metabolism alteration in ocular surface epithelial cells in the course of DED. Our aim was to explore the effects of benzalkonium chloride or hyperosmolarity exposure on the human corneal epithelial (HCE) cell lipidome, two different conditions used as in vitro models of DED. For this purpose, we performed a lipidomic analysis using UPLC-HRMS-ESI+/−. Our results demonstrated that BAK or hyperosmolarity induced important modifications in HCE lipidome including major changes in sphingolipids, glycerolipids and glycerophospholipids. For both exposures, an increase in ceramide was especially exhibited. Hyperosmolarity specifically induced triglyceride accumulation resulting in lipid droplet formation. Conversely, BAK induced an increase in lysophospholipids and a decrease in phospholipids. This lipidomic study highlights the lipid changes involved in inflammatory responses following BAK or hyperosmolarity exposures. Thereby, lipid research appears of great interest, as it could lead to the discovery of new biomarkers and therapeutic targets for the diagnosis and treatment of dry eye disease.     

Biophysical investigations of the structure and function of the tear fluid lipid layers and the effect of ectoine. Part B: Artificial lipid films

The tear fluid lipid layer is present at the outermost part of the tear film which lines the ocular surface and functions to maintain the corneal surface moist by retarding evaporation. Instability in the structure of the tear fluid lipid layer can cause an increased rate of evaporation and thus dry eye syndrome. Ectoine has been previously shown to fluidize lipid monolayers and alter the phase behavior. In the current study we have investigated the effect of ectoine on the artificial tear fluid lipid layer composed of binary and ternary lipid mixtures of dipalmitoyl phosphatidylcholine (DPPC), cholesteryl esters and tri-acyl-glycerols. The focus of our study was mainly the structural and the biophysical aspects of the artificial tear fluid lipid layer using surface activity studies and topology analysis. The presence of ectoine consistently causes an expansion of the pressure–area isotherm indicating increased intermolecular spacing. The topology studies showed the formation of droplet-like structures due to the addition of ectoine only when tri-acyl-glycerol is present in the mixture of DPPC and chol-palmitate, similar to the natural meibomian lipids. Consequently, the hypothesis of an exclusion of tri/di-acyl-glycerol from the meibomian lipid film in the presence of ectoine in the subphase is confirmed. A model describing the effect of ectoine on meibomian lipid films is further presented which may have an application for the use of ectoines in eye drops as a treatment for the dry eye syndrome.     

Meniscal Tear Film Fluid Dynamics Near Marx’s Line

Extensive studies have explored the dynamics of the ocular surface fluid, though theoretical investigations are typically limited to the use of the lubrication approximation, which is not guaranteed to be uniformly valid a-priori throughout the tear meniscus. However, resolving tear film behaviour within the meniscus and especially its apices is required to characterise the flow dynamics where the tear film is especially thin, and thus most susceptible to evaporatively induced hyperosmolarity and subsequent epithelial damage. Hence, we have explored the accuracy of the standard lubrication approximation for the tear film by explicit comparisons with the 2D Navier–Stokes model, considering both stationary and moving eyelids. Our results demonstrate that the lubrication model is qualitatively accurate except in the vicinity of the eyelids. In particular, and in contrast to lubrication theory, the solution of the full Navier–Stokes equations predict a distinct absence of fluid flow, and thus convective mixing in the region adjacent to the tear film contact line. These observations not only support emergent hypotheses concerning the formation of Marx’s line, a region of epithelial cell staining adjacent to the contact line on the eyelid, but also enhance our understanding of the pathophysiological consequences of the flow profile near the tear film contact line.     

Longitudinal changes in tear fluid lipidome brought about by eyelid-warming treatment in a cohort of meibomian gland dysfunction

Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye and ocular discomfort characterized by an unstable tear film principally attributed to afflicted delivery of lipids to the ocular surface. Herein, we elucidated longitudinal tear lipid alterations associated with disease alleviation and symptom improvement in a cohort of MGD patients undergoing eyelid-warming treatment for 12 weeks. Remarkably, eyelid-warming resulted in stark reductions in lysophospholipids (P < 0.001 for lyso-plasmalogen phosphatidylethanolamine, lysophosphatidylcholine, and lysophosphatidylinositol), as well as numerous PUFA-containing diacylglyceride species in tears, accompanied by significant increases in several PUFA-containing phospholipids. These changes in tear lipidomes suggest that eyelid-warming leads to diminished activity of tear phospholipases that preferentially target PUFA-containing phospholipids. In addition, treatment led to appreciable increases (P < 0.001) in O-acyl-ω-hydroxy-FAs (OAHFAs), which are lipid amphiphiles critical to the maintenance of tear film stability. Longitudinal changes in the tear lipids aforementioned also significantly (P < 0.05) correlated with reduced rate of ocular evaporation and improvement in ocular symptoms. The foregoing data thus indicate that excess ocular surface phospholipase activity detrimental to tear film stability could be alleviated by eyelid warming alone without application of steroids and identify tear OAHFAs as suitable markers to monitor treatment response in MGD.     

Assessment of thermal dehydration using the human eye: What is the potential?

Human hydration assessment is a key component for the prevention and proper treatment of heat-related fluid and electrolyte imbalances within military, sports and clinical medicine communities. Despite the availability of many different methods for assessing hydration status, the need for a valid method or technology that is simple, rapid, non-invasive, universal (detects both hypertonic and isotonic hypovolaemia) and is applicable for static (single point in time) and dynamic (change across time) hydration assessment is widely acknowledged. The eye is one candidate body region that might afford such a measure given the intricate balance between ocular dynamics (tear and aqueous humor formation) and blood (plasma osmolality and volume), which is considered the criterion measure for hydration assessment. The aim of this review is to introduce and discuss the potential for using ocular measurements for non-invasive hydration assessment, including tear fluid osmolarity (Tosm), non-invasive tear break-up time (NITBUT) and intraocular pressure (IOP). There is a relevant physiological basis for testing the merit of ocular measures for human hydration assessment and recent data indicate that Tosm and IOP may have utility. Further investigations are warranted to determine the degree to which ocular measures can act as accurate and reliable non-invasive hydration status markers.     

Identification of 491 proteins in the tear fluid proteome reveals a large number of proteases and protease inhibitors

Background  

The tear film is a thin layer of fluid that covers the ocular surface and is involved in lubrication and protection of the eye. Little is known about the protein composition of tear fluid but its deregulation is associated with disease states, such as diabetic dry eyes. This makes this body fluid an interesting candidate for in-depth proteomic analysis.     

Mucins and TFF peptides of the tear film and lacrimal apparatus

The three-dimensional organization of the tear film, which is produced and drained by the different structures of the ocular adnexa, is essential for maintainance and protection of the ocular surface. This is facilitated by a class of large, highly glycosylated, hydrophilic glycoproteins, the mucins, which are usually expressed in association with a class of peptides having a well-defined, structurally conserved trefoil domain, the mammalian trefoil factor family (TFF) peptides. In this review, the latest information regarding mucin and TFF peptide function and regulation in the human lacrimal system, the tear film and the ocular surface is summarized with regard to mucous epithelia integrity, rheological and antimicrobial properties of the tear film and tear outflow, age-related changes and certain disease states such as dry eye, dacryostenosis and dacryolith formation.     

Elastohydrodynamics of the Eyelid Wiper

This paper presents an elastohydrodynamic model of the human eyelid wiper. Standard lubrication theory is applied to the fluid layer between the eyelid wiper and ocular surface. The role of the lubrication film is to reduce the shear stresses by preventing solid to solid contact between the eyelid wiper and ocular surface. For the lubrication film to be effective, it is required that the orientation of the eyelid wiper changes between the opening and closing phases of a blink. In order to model this, the hydrodynamic model is coupled with an elastic mattress model for the soft tissue of the eyelid wiper and ocular surface. This leads to a one-dimensional non-linear partial differential equation governing the fluid pressure in the lubrication film. In order to solve the differential equation, a loading condition or constraint equation must be specified. The resulting system is then solved numerically. The model allows predictions of the tear film flux from under the upper eyelid, as well as normal and shear stresses acting on the ocular surface. These factors are important in relation to dry eye syndrome, deformation of the cornea and contact lens design. It is found that the pressure and shear stress under the eyelid act across a length of approximately 0.1 mm which is consistent with clinical observations. It order to achieve a flow of tears from under the upper eyelid during a blink, the model requires that the normal force the eyelid applies to the ocular surface during the closing phase of the blink is significantly higher than during the opening phase of the blink. Electronic Supplementary Material The online version of this article () contains supplementary material, which is available to authorized users.     

Biophysical properties of tear film lipid layer I. Surface tension and surface rheology

Tear film lipid layer (TFLL) is the outmost layer of the tear film. It plays a crucial role in stabilizing the tear film by reducing surface tension and retarding evaporation of the aqueous layer. Dysfunction of the TFLL leads to dysfunctional tear syndrome, with dry eye disease (DED) being the most prevalent eye disease, affecting 10%–30% of the world population. To date, except for treatments alleviating dry eye symptoms, effective therapeutic interventions in treating DED are still lacking. Therefore, there is an urgent need to understand the biophysical properties of the TFLL with the long-term goal to develop translational solutions in effectively managing DED. Here, we studied the composition-function correlations of an artificial TFLL, under physiologically relevant conditions, using a novel experimental methodology called constrained drop surfactometry. This artificial TFLL was composed of 40% behenyl oleate and 40% cholesteryl oleate, representing the most abundant wax ester and cholesteryl ester in the natural TFLL, respectively, and 15% phosphatidylcholine and 5% palmitic-acid-9-hydroxy-stearic-acid (PAHSA), which represent the two predominant polar lipid classes in the natural TFLL. Our study suggests that the major biophysical function of phospholipids in the TFLL is to reduce the surface tension, whereas the primary function of PAHSA is to optimize the rheological properties of the TFLL. These findings have novel implications in better understanding the physiological and biophysical functions of the TFLL and may offer new translational insight to the treatment of DED.     

Phospholipid transfer protein is present in human tear fluid

The human tear fluid film consists of a superficial lipid layer, an aqueous middle layer, and a hydrated mucin layer located next to the corneal epithelium. The superficial lipid layer protects the eye from drying and is composed of polar and neutral lipids provided by the meibomian glands. Excess accumulation of lipids in the tear film may lead to drying of the corneal epithelium. In the circulation, phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) mediate lipid transfers. To gain insight into the formation of tear film, we investigated whether PLTP and CETP are present in human tear fluid. Tear fluid samples were collected with microcapillaries. The presence of PLTP and CETP was studied in tear fluid by Western blotting, and the PLTP concentration was determined by ELISA. The activities of the enzymes were determined by specific lipid transfer assays. Size-exclusion and heparin-affinity chromatography assessed the molecular form of PLTP. PLTP is present in tear fluid, whereas CETP is not. Quantitative assessment of PLTP by ELISA indicated that the PLTP concentration in tear fluid, 10.9 +/- 2.4 microg/mL, is about 2-fold higher than that in human plasma. PLTP-facilitated phospholipid transfer activity in tears, 15.1 +/- 1.8 micromol mL(-)(1) h(-)(1), was also significantly higher than that measured in plasma. Inactivation of PLTP by heat treatment (+58 degrees C, 60 min) or immunoinhibition abolished the phospholipid transfer activity in tear fluid. Size-exclusion chromatography of tear fluid indicated that PLTP eluted in a position corresponding to a size of 160-170 kDa. Tear fluid PLTP was quantitatively bound to Heparin-Sepharose and could be eluted as a single peak by 0.5 M NaCl. These data indicate that human tear fluid contains catalytically active PLTP protein, which resembles the active form of PLTP present in plasma. The results suggest that PLTP may play a role in the formation of the tear film by supporting phospholipid transfer.     

The Effect of Tear Supplementation on Ocular Surface Sensations during the Interblink Interval in Patients with Dry Eye

Purpose

To investigate the characteristics of ocular surface sensations and corneal sensitivity during the interblink interval before and after tear supplementation in dry eye patients.

Methods

Twenty subjects (41.88±14.37 years) with dry eye symptoms were included in the dry eye group. Fourteen subjects (39.13±11.27 years) without any clinical signs and/or symptoms of dry eye were included in the control group. Tear film dynamics was assessed by non-invasive tear film breakup time (NI-BUT) in parallel with continuous recordings of ocular sensations during forced blinking. Corneal sensitivity to selective stimulation of corneal mechano-, cold and chemical receptors was assessed using a gas esthesiometer. All the measurements were made before and 5 min after saline and hydroxypropyl-guar (HP-guar) drops.

Results

In dry eye patients the intensity of irritation increased rapidly after the last blink during forced blinking, while in controls there was no alteration in the intensity during the first 10 sec followed by an exponential increase. Irritation scores were significantly higher in dry eye patients throughout the entire interblink interval compared to controls (p<0.004). NI-BUT significantly increased after HP-guar (p = 0.003) but not after saline drops (p = 0.14). In both groups, either after saline or HP-guar the shape of symptom intensity curves remained the same with significantly lower irritation scores (p<0.004), however after HP-guar the decrease was significantly more pronounced (p<0.004). Corneal sensitivity to selective mechanical, cold and chemical stimulation decreased significantly in both groups after HP-guar (p<0.05), but not after saline drops (p>0.05).

Conclusion

Ocular surface irritation responses due to tear film drying are considerably increased in dry eye patients compared to normal subjects. Although tear supplementation improves the protective tear film layer, and thus reduce unpleasant sensory responses, the rapid rise in discomfort is still maintained and might be responsible for the remaining complaints of dry eye patients despite the treatment.     

Tear cytokine and ocular surface alterations following brief passive cigarette smoke exposure

Purpose: To prospectively investigate the effects of acute passive cigarette smoke exposure on the ocular surface and tear film in healthy non-smokers. Methods: Twelve right eyes of 12 subjects without any ocular diseases were examined before, 5 min, and 24 h after 5 min of passive cigarette smoke exposure in a controlled smoke chamber. Tear samples were obtained before, 5 min and 24 h after smoke exposure to detect tear hexanoyl-lysine (HEL), acrolein and inflammatory cytokine concentrations. Tear evaporation rate, DR-1 tear film lipid layer interferometry, tear film break-up time (TBUT), ocular surface fluorescein staining (FS) and Rose Bengal staining (RB), Schirmer I test were performed before, 5 min, and 24 h after smoke exposure. Conjunctival impression cytology (IC) and brush cytology (BC) were carried out before and 24 h after smoke exposure. Results: Tear evaporation rate, tear lipid spread time, tear film break-up time, and vital staining scores showed significant worsening with passive smoke exposure. Tear HEL and IL-6 concentrations increased significantly 24 h after smoke exposure. Tear acrolein level showed an insignificant increase at 5 min. IC and RT-PCR revealed a significant reduction in goblet cell density, a shift toward higher squamous metaplasia grades and a significant downregulation of MUC5AC mRNA expression at 24 h. Conclusion: Even brief passive exposure to cigarette smoke in healthy non-smoker subjects was associated with adverse effects on the ocular surface health as evidenced by an increase of tear inflammatory cytokines, tear lipid peroxidation products and decrease of mucosal defense resulting in tear instability and damage to the ocular surface epithelia.     

Identification of hemopexin in tear film

Human tear fluid is a complex mixture of aqueous lipids, proteins, enzymes, and other biochemical and cellular elements. By conventional comparative proteomic approaches, we investigated the proteome in human tear fluid and compared the tear protein profile of normal control subjects with that of patients suffering from the ocular inflammatory disease vernal keratoconjunctivitis (VKC). Collected tear samples were directed to two-dimensional polyacrylamide gel electrophoresis protein separation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry peptide identification. Six differentially expressed proteins—interleukin 4, phospholipase A2, albumin, lactoferrin, hemopexin, and lipocalin—were displayed. Hemopexin had not been reported previously in tear film. Enzyme-linked immunosorbent assay confirmed that hemopexin concentrations were significantly higher in VKC tear samples and increased with disease stages. The results implied clinical interest of hemopexin in the tear proteome and eye diseases.     

Hyperosmolarity‐mediated mitochondrial dysfunction requires Transglutaminase‐2 in human Corneal epithelial cells

Hyperosmolar‐induced ocular surface cell death is a key mitochondria‐mediated event in inflammatory eye diseases. Transglutaminase (TGM)‐2, a cross‐linking enzyme, is purported to mediate cell death, but its link to mitochondria is unclear. In the cornea, the integrity of the epithelial cells is important for maintaining transparency of the cornea and therefore functional vision. We evaluated the role of TGM‐2 and its involvement in hyperosmolarity‐stimulated mitochondrial cell death in human corneal epithelial (HCE‐T) cells. HCE‐T cell lines stably expressing either shRNA targeting TGM‐2 (shTG) or scrambled shRNA (shRNA) were constructed. Hyperosmolar conditions reduced viability and increased mitochondrial depolarization in shRNA cells. However, hyperosmolarity failed to induce mitochondrial depolarization to the same extent in shTG cells. Transient overexpression of TGM‐2 resulted in very high levels of TGM‐2 expression in shTG and shRNA cells. In the case of shTG cells after overexpression of TGM‐2, hyperosmolarity induced the same extent of mitochondrial depolarization as similarly treated shRNA cells. Overexpression of TGM‐2 also elevated transamidase activity and reduced viability. It also induced mitochondrial depolarization, increased caspase‐3/7 and ‐9 activity, and these increases were partially suppressed by pan‐caspase inhibitor Z‐VAD‐FMK. Corneal epithelial apoptosis via mitochondrial dysfunction after hyperosmolar stimulation is partially dependent on TGM‐2. This TGM‐2‐dependent mechanism occurs in part via caspase‐3/7 and ‐9. Protection against mitochondrial stress in the ocular surface targeting TGM‐2 may have important implications in the survival of cells in hyperosmolar stress. J. Cell. Physiol. 226: 693–699, 2011. © 2010 Wiley‐Liss, Inc.     

Environmental light and endogenous antioxidants as the main determinants of non-cancer ocular diseases

The human eye is constantly exposed to sunlight and artificial lighting. Exogenous sources of reactive oxygen species (ROS) such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins contribute to oxidative damage in ocular tissues. Long-term exposure to these insults places the aging eye at considerable risk for pathological consequences of oxidative stress. Furthermore, in eye tissues, mitochondria are an important endogenous source of ROS. Over time, all ocular structures, from the tear film to the retina, undergo oxidative stress, and therefore, the antioxidant defenses of each tissue assume the role of a safeguard against degenerative ocular pathologies. The ocular surface and cornea protect the other ocular tissues and are significantly exposed to oxidative stress of environmental origin. Overwhelming of antioxidant defenses in these tissues clinically manifests as pathologies including pterygium, corneal dystrophies, and endothelial Fuch's dystrophy. The crystalline lens is highly susceptible to oxidative damage in aging because its cells and their intracellular proteins are not turned over or replaced, thus providing the basis for cataractogenesis. The trabecular meshwork, which is the anterior chamber tissue devoted to aqueous humor drainage, has a particular susceptibility to mitochondrial oxidative injury that affects its endothelium and leads to an intraocular pressure increase that marks the beginning of glaucoma. Photo-oxidative stress can cause acute or chronic retinal damage. The pathogenesis of age-related macular degeneration involves oxidative stress and death of the retinal pigment epithelium followed by death of the overlying photoreceptors. Accordingly, converging evidence indicates that mutagenic mechanisms of environmental and endogenous sources play a fundamental pathogenic role in degenerative eye diseases.     

The Effect of Polar Lipids on Tear Film Dynamics

In this paper, we present a mathematical model describing the effect of polar lipids, excreted by glands in the eyelid and present on the surface of the tear film, on the evolution of a pre-corneal tear film. We aim to explain the interesting experimentally observed phenomenon that the tear film continues to move upward even after the upper eyelid has become stationary. The polar lipid is an insoluble surface species that locally alters the surface tension of the tear film. In the lubrication limit, the model reduces to two coupled non-linear partial differential equations for the film thickness and the concentration of lipid. We solve the system numerically and observe that increasing the concentration of the lipid increases the flow of liquid up the eye. We further exploit the size of the parameters in the problem to explain the initial evolution of the system.     

Biophysical investigations of the structure and function of the tear fluid lipid layer and the effect of ectoine. Part A: Natural meibomian lipid films

The tear fluid lipid layer is the outermost part of the tear film on the ocular surface which protects the eye from inflammations and injuries. We investigated the influence of ectoine on the structural organization of natural meibomian lipid films using surface activity analysis and topographical studies. These films exhibit a continuous pressure–area isotherm without any phase transition. With the addition of ectoine, the isotherm is expanded towards higher area per molecule values suggesting an increased area occupied by the interfacial lipid molecules. The AFM topology scans of natural meibomian lipid films reveal a presence of fiber-like structures. The addition of ectoine causes an appearance of droplet-like structures which are hypothesized to be tri-acyl-glycerols and other hydrophobic components excluded from the lipid film. Further the material properties of the droplet-like structure with respect to the surrounding were determined by using the quantitative imaging mode of the AFM technique. The droplet-like structures were found to be comparatively softer than the surrounding. Based on the observations a preliminary hypothesis is proposed explaining the mechanism of action of ectoine leading to the fluidization of meibomian lipid films. This suggests the possibility of ectoine as a treatment for the dry eye syndrome.     

Corneal cell proteins and ocular surface pathology

The cornea is a transparent and avascular tissue that functions as the major refractive structure for the eye. A wide variety of growth factors, chemokines, cytokines and their receptors are synthesized by corneal epithelial and stromal cells, and are found in tears. These molecules function in corneal wound healing and in inflammatory responses. Proteoglycans and glycoproteins are essential for normal corneal function, both at the air-epithelial interface and within the extracellular matrix. The ocular MUC mucins may play roles in forming the mucus layer of the tear film, in regulating tear film spread, and in inhibiting the adhesion of pathogens to the ocular surface. Lumican, keratocan and mimecan are the major keratan sulfate proteoglycans of the corneal stroma. They are essential, along with other proteoglycans and interfibrillar proteins, including collagens type VI and XII, for the maintenance of corneal transparency. Corneal epithelial cells interact with a specialized extracellular matrix structure, the basement membrane, composed of a specific subset of collagen type IV and laminin isoforms in addition to ubiquitous extracellular matrix molecules. Matrix metalloprotein-ases have been identified in normal corneal tissue and cells and may play a role in the development of ulcerative corneal diseases. Changes in extracellular matrix molecule localization and synthesis have been noted in other types of corneal diseases as well, including bullous keratopathy and keratoconus.     

Role of lactoferrin in the tear film

The surface of the eye provides an inert barrier against infection. Through its unique combination of antimicrobial action and anti-inflammatory activities lactoferrin (Lf) in the tear film plays an important role in the maintenance of ocular health. In order to maintain clarity the eye must provide immunological defense without immunopathology. Along with physical barriers, soluble plasma factors and other proteins such as lysozyme, Lf produced by the acinar cells of the lacrimal gland serves a number of roles in defense for this purpose. Lf in tears provides antimicrobial efficacy by binding free iron thus reducing the availability of iron necessary for microbial growth and survival as well as pathogenesis. Lf has been shown to inhibit biofilm formation and thus may play a role in protecting contact lens surfaces from colonization. Virus particles' entry into epithelial cells is inhibited by Lf while an excess of Lf in tear film is thought to limit the opportunistic Lf-mediated bridging of adenovirus and host cell that occurs in other tissues. Lf dampens the classical complement activation pathway by binding to markers of inflammation and immune activation while pathogen-associated molecular patterns such as lipopolysaccharide (LPS) are targeted by Lf for removal through tears and hydrodynamic flushing. This review focuses on the role of Lf in human tear film and its contribution to ocular health during contact lens wear.