• dry eye;
  • osmolality of tears;
  • tears


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  2. Abstract

The tear film is a nourishing, lubricating and protecting layer that bathes the ocular surface. It is continuously replenished through cycles of production and elimination via evaporation, absorption and drainage. These processes are often referred to as tear film dynamics. Osmolality is an objective clinical measurement that provides insight into the balance of these complex tear film dynamics. Balanced tear production and elimination is vital for tear film integrity, stability and normal osmolality. Imbalances cause alterations of the tear film structure and composition, ultimately leading to tear film instability and measurable tear film hyperosmolality. Elevated tear film osmolality is considered a core mechanism in dry eye, forming the basis of dry eye symptoms and leading to ocular surface damage. Despite its immense potential in the diagnosis of dry eye, tear film osmolality is not commonly assessed. This review will focus on the current knowledge of tear film dynamics and tear film osmolality.

The pre-ocular tear film is the outermost layer of the eye and is of critical importance to the health of the ocular surface. A continuous cycle of production, evaporation, absorption and drainage leads to a dynamic equilibrium in the pre-ocular tear film. Tear film osmolality or tear saltiness can be considered a consequence of these various factors in tear film dynamics.1 Homeostatic balance leads to tear film stability, enabling the tear film to fulfil its vital functions such as lubrication, nourishment and protection of the ocular surface.2,3 Homeostatic imbalance causes alteration of the tear film structure and composition, ultimately leading to tear film instability and tear film hyperosmolality.2 Measurement of tear film osmolality has been suggested as a gold standard in the diagnosis of dry eyes as elevated tear film osmolality is considered a core mechanism in symptoms and ocular surface damage in dry eye.2,4,5

Despite its immense potential in the diagnosis of dry eye, measurement of tear film osmolality has not been amenable to in-office use and is largely confined to use in research. Newly available technology might increase its uptake by clinicians. This review focuses on the current knowledge of tear film dynamics and the relevance and clinical implications of tear film osmolality.


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  2. Abstract

The classical description of the tear film is a three-layered structure, with a predominant aqueous phase, a superficial thin oily layer, which interfaces with the environment, and a deep mucous layer at the base.6,7 The thickness of the tear film was originally estimated to be 4 to 8 µm, with the aqueous layer being the thickest layer (7 µm) and the lipid and mucous layers each relatively thin at 0.1 and 0.05 µm, respectively.6,8,9 Using non-invasive laser interferometry and confocal microscopy, Prydal and colleagues10 measured a tear film thickness of approximately 40 µm and attributed this new thickness to previous underestimations of the mucin layer. These thickness measurements contributed to the current tear film model, a bi-layer model, in which the aqueous phase and mucous layer create a gel mixture with decreasing mucin concentration from the epithelium to the lipid layer.11 As reviewed by King-Smith and colleagues,12 current estimations of the thickness of the pre-ocular tear film range between 3 and 11 µm.

The mucous layer, produced by the goblet cells and corneal and conjunctival epithelia, is composed of secreted and transmembrane mucins, immunoglobulins, salts, urea, enzymes, glucose and leukocytes.13,14 Transmembrane mucins form a dense hydrophilic barrier, protecting the ocular surface against adherence of pathogens and debris and increasing stability of the overlying tear film through increased wettability. These mucins contribute to tear stability and regulation of epithelial growth and might be involved in cellular signalling.14,15 The gel-like barrier facilitates movement of the lids and globe without shearing damage, transport of pathogens and particles away from the surface, and movement of proteins.14

Primarily produced by the main lacrimal gland and by the accessory lacrimal glands of Krause and Wolfring, the aqueous layer consists of water, electrolytes, proteins, anti-microbial agents, cytokines, vitamins, immunoglobulins, peptide growth factors and hormones. The aqueous layer is the thickest layer and its functions include lubricating the ocular surface, washing away foreign bodies and nourishing the avascular cornea with oxygen, proteins and inorganic salts. Between 60 and 500 different proteins have been identified in the tear film.16,17 The primary tear film proteins include lysozyme, lactoferrin and lipocalin, which together with immunoglobulins, defensins and glycoproteins are responsible for anti-microbial activity and defence.13,18,19 Growth factors, vitamins and electrolytes are essential for maintaining ocular health and epithelial integrity.

The lipid layer, the outermost layer of the tear film, is secreted primarily by the tubule-acinar holocrine meibomian glands, with some small contribution by the glands of Moll and Zeiss and possibly the lacrimal glands and epithelial cells.19,20 Polar lipids such as phospholipids and sphingolipids form a thin polar-surfactant layer. Non-polar lipids such as wax esters, sterol esters and triglycerides form the thick outer layer.21 It is postulated that the main function of the lipid layer is to reduce evaporation of the underlying aqueous phase in the open eye.22,23 Additional functions of the lipid layer are to provide a smooth optical surface, to limit contamination of the eye from particles and organisms such as dust and bacteria, to avoid contamination of the tear film by skin lipids, as these lipids differ in composition and might cause destabilisation of the tear film, to reduce the surface tension of the aqueous phase enabling spreading of the lipid layer over the aqueous phase and to avoid spilling of tears onto the skin.24–27


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  2. Abstract

Tear secretion

Production of the tear film is a highly complex process, controlled mainly by the lacrimal functional unit, which comprises the main and accessory lacrimal glands, the ocular surface (cornea, conjunctiva and meibomian glands), the eyelids and the interconnecting sensory and motor nerves.28,29 Basal tear secretion and reflex tearing occur in response to challenges resulting from stimulation of the free nerve endings in the densely innervated cornea and to some degree from stimulation of the conjunctiva.27,28 Stimulation of the individual tear secretion glands is also influenced by a range of hormones and cytokines.19 Alterations of any component of the lacrimal functional unit or of the hormonal or cytokine balance might result in compromised tear film secretion leading to an imbalance in tear dynamics.

Tear film evaporation

The tear film interfaces with the environment and thus is subject to evaporation. Similar to their effects on an exposed water surface, environmental factors such as humidity, temperature and air movement affect the rate of evaporation from the ocular surface.30,31 Evaporation of the tear film is significantly slowed by an intact lipid layer with evaporation increasing at least four-fold if the lipid layer is absent or compromised.22,23,32 Tear film evaporation rates range between 1.4 and 39.3 × 10-7 g/cm2/s.33,34 Recently, tear film interferometry has been introduced in the investigation of tear film evaporation, demonstrating evaporation rates five-times higher than those measured using previous techniques.35,36 This discrepancy might arise from free air circulation in front of the eye when using interferometry in contrast to the potentially restricted evaporation caused by a thick humid air layer, which develops within the ocular chamber used in previous techniques.35 Techniques applying an ocular chamber with ‘ventilation’ and in vitro measurements support the results obtained by interferometry.30,37 Higher evaporation rates would have considerable impact on tear film dynamics, stability and osmolality, suggesting that evaporation could be a major contributor to tear film thinning and hence tear film instability and hyperosmolality.35

Tear film drainage

Notwithstanding the recent findings on tear film evaporation, the majority of tear fluid drains through the lacrimal puncta.38,39 Elimination of tears through the lacrimal drainage system allows removal of cellular debris, toxins, inflammatory cells and other waste products and is of vital importance to ocular surface health.40 With each blink, tears are moved nasally and towards the puncta.41 Tears are moved into the lacrimal puncta by negative pressure created within the lacrimal drainage system during a blink.42 The majority of tears drain through the lower puncta;43,44 however, if drainage is impaired in the lower puncta, sufficient drainage can be obtained through the upper puncta.42,45,46 Finally, tears move via gravity from the upper tear meniscus to the lower one. In the presence of impaired drainage, reduced tear production has been observed.47–49 This regulatory mechanism between the lacrimal drainage tract, the ocular surface and the lacrimal gland was confirmed in studies using punctal plugs and has been further supported by the lack of constant epiphora in patients with primary acquired nasolacrimal duct obstruction.50–52 This feedback mechanism between drainage and production of tears highlights the importance of tear elimination via drainage in the model of tear dynamics.

Tear absorption

Contributing to tear film dynamics, tear film absorption occurs via the cornea, conjunctiva and epithelium of the nasolacrimal duct. Most absorption occurs in the tissue of the nasolacrimal duct, while absorption via the cornea and conjunctiva plays only a minor role, possibly due to the tight junctions in these tissues.41


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  2. Abstract

Definition of osmolality

Osmolality is defined as the total number of dissolved solute particles in one kilogram of solution, without consideration of the nature of the particles, that is, their shape, size, density, configuration or charge. Another term often used for the saltiness of tears is osmolarity. Both osmolality and osmolarity refer to the amount of osmotically active particles; however, small differences exist between the two terms. Osmolarity is defined as the number of osmoles per litre of solution and due to a change in solution volume with temperature and in contrast to osmolality it is temperature dependent.53 Additionally, the volume of the solute particles in a solution will create a difference between osmolality and osmolarity, resulting in a higher osmolality than osmolarity. This difference increases with more concentrated solutions; however, while this is of importance for some body fluids, such as blood plasma, the protein content in tears is relatively low so that the osmolarity of the tear film is only five per cent lower than its osmolality. This difference is often regarded as clinically irrelevant.54

In its strictest sense, the osmolarity of a solution cannot be determined experimentally and must be calculated, in contrast to osmolality, which can be determined experimentally using available osmometers.53 Calculations of osmolality and osmolarity are not always straightforward. Due to incomplete dissociation and solute–solution interaction, the calculated (ideal) osmolality might differ from the measured (actual) one.53

Measurement of osmolality

Osmolality measurements are based on the determination of one of the four colligative properties of a solution, that is, freezing point, boiling point, vapour pressure and osmotic pressure. The addition of a solute alters the chemical potential of a solvent and leads to a change of the colligative properties of the solvent, such that the freezing point and vapour pressure will decrease, while the boiling point and osmotic pressure will increase. A relationship between the solvent chemical potential and the colligative properties forms the basis for osmolality measurements of tears and other solutions.55

Although osmolality measurements via boiling point or osmotic pressure are theoretically possible, limitations in suitable membranes and solution instability at high temperatures limit these applications. Therefore, traditionally, the osmolality of tears is determined mainly via freezing point depression and vapour pressure.

Adding 1.0 mol of solute to 1.0 kg of solution will lower the freezing point by 1.86°C.55 Freezing point osmometers rely on the correlation between osmolality and the depression in freezing point by addition of solute to the solvent. To determine the osmolality of a solution, the sample is supercooled (significantly below its expected freezing point). During the crystallisation process, heat of fusion is released and the solution reaches a plateau in temperature for a moment. This temperature is measured and translated into the corresponding osmolality of the solution. Due to the measurement technique used, freezing point osmometers are not suitable for highly viscous solutions. Additionally, the correlation between freezing point depression and osmolality is complex, resulting in a possible departure of the measured osmolality from the actual one. Particularly for highly concentrated solutions, deviations between actual and measured osmolality can occur due to mathematical simplifications and assumptions in the derivation of the osmolality from the measured freezing point.55

Measurements via vapour pressure depression are based on the correlation between osmolality and the depression in vapour pressure by addition of solute to the solvent. Adding 1.0 mol of solute to 1.0 kg of solution will decrease the vapour pressure by 0.3 mmHg.56 The osmolality of a solution is measured via a fine-wire thermocouple hygrometer that determines the dew point temperature depression of the solution. To measure the osmolality of a solution, the temperature of the solution is equilibrated and taken as a reference value. Subsequently, the thermocouple is cooled, which leads to formation of water droplets on the thermocouple. A control mechanism is applied ensuring that the thermocouple's temperature is solely affected by the condensing water droplets. Condensing will cease once the thermocouple reaches the dew point temperature and the difference to the original reference temperature serves for the calculation of the solution's osmolality. Although osmolality measurements using vapour pressure osmometry are often regarded as ideal, there are limitations to this technique. Accurate measurements of solutions containing volatile substances are impossible due to the evaporation of solutes. Additionally, measurements with a vapour pressure osmometer were less repeatable and seem to differ from measurements with a freezing point depression osmometer.57

Determinations of tear osmolality via tear fluid conductivity58 or with a new ‘chip-based osmometer’59 allow in vivo measurements. This is in contrast to measurements with a freezing point depression or a vapour pressure osmometer, which can be obtained only from collected tears. Although both the freezing point depression and the vapour pressure osmometers have their limitations, particularly for highly concentrated and very complex solutions, currently these instruments are used mainly for the determination of tear film osmolality. In the past, freezing point osmometers were seen as superior to vapour pressure osmometers due to their small fluid requirements, which also brought them the synonym ‘nanolitre osmometers’.

Osmolality of the tear film

Osmolality of the tear film is an index of the tear dynamics and represents a value for the balance of tear production, evaporation, drainage and absorption.1 Measurements of tear osmolality in normal, non-diseased eyes date back to 1841 and have been summarised by Murube.54 Tomlinson and colleagues60 reviewed studies determining tear film osmolality in normal, non-dry eyes and found the average value to be approximately 302 mmol/kg.

Tear osmolality is determined mainly by the electrolytes of the aqueous phase of the tear film, with proteins and sugars being minor contributors.54,61 Due to their low concentration and high molecular weight, the colloidal osmolality of tear proteins and sugars approximates 2.0 mmHg and therefore is less than one per cent of the total tear film osmolality.62 Of the electrolytes present in the tear film, the cations sodium and potassium, and the anions chloride and bicarbonate are the major contributors to tear osmolality63 (Table 1).

Table 1. Main concentration of electrolytes in the tear film
Concentration in mmol/kgµmol/kgmmol/kg

The main lacrimal gland, the accessory lacrimal glands of Krause and Wolfring, the cornea and the conjunctiva are responsible for the secretion of electrolytes into the aqueous phase of the tear film. Electrolytes play an essential role in the maintenance of the integrity of the epithelium and provide a buffering capacity to the pH of the tear film.64,65 In the main lacrimal gland, the acinar cells, which form the primary component of the lacrimal gland, secrete electrolytes and water in a composition similar to plasma. As the fluid passes the ducts it is modified by either the addition of chloride and potassium or water absorption.66,67 Secretion from the main lacrimal gland is stimulated by three different cellular signal transduction pathways, which stimulate a release and activation of proteins involved in the final secretion of tear film electrolytes and proteins.19,68 Little is known about the electrolyte and water secretion of the accessory glands and the corneal and conjunctival epithelia. The accessory glands and corneal epithelium appear to secrete electrolytes and water through neural regulation and usage of the cAMP-dependent pathway. The secretion of tears by the conjunctival epithelium remains unknown.68 In addition to the secretion of water and electrolytes, transport of water through the conjunctiva and cornea via aquaporin channels has been suggested.69,70

Controversy has evolved around the impact of the tear flow rate on electrolyte secretion and osmolality. Some authors demonstrated a constant osmolality and secretion of sodium, bicarbonate and chloride ions independent of the tear flow rate.63,71 Botelho and Martinez72 demonstrated a constant flow of sodium and chloride between 2 and 30 µl/min, but an increase in concentration if the flow rate was less than 0.5 µl/min. The dependence of potassium secretion on the flow rate remains equivocal.63,71,72 Although calcium is only a minor contributor to osmolality, an increase in concentration occurs if the flow rate falls below 2.0 µl/min, but otherwise it is independent of the flow rate.73 Gilbard and Dartt74 investigated the osmolality of lacrimal gland fluid over a range of flow rates in rabbits and demonstrated an elevation of tear osmolality with decreasing flow rates. Therefore, if tears are collected for osmolality measurements, collection should occur without inducing reflex tearing and without a biomicroscope because this can lower the osmolality of tears due to an increased flow rate.75,76

Osmolality of the tear film results from a combination of all electrolytes secreted from different sources and differs across the ocular surface and throughout the day. Tear film osmolality is reduced after prolonged lid closure and sleep, and shows a trend towards increased osmolality during the day.77–80 The osmolality of tears sampled from the inferior tear meniscus might underestimate the osmolality of the tear fluid across the cornea due to the variable effects of evaporation.81 Benjamin and Hill82,83 were able to demonstrate differences in osmolality among ocular sites and between the inferior tear meniscus and the cul-de-sac.

Although small differences in tear film osmolality have been observed between men and women, there is general agreement that gender does not affect tear film osmolality.79,84,85 An effect of age on tear osmolality has been reported in women, but was attributed to the low osmolality values obtained for young women.84 Mathers and colleagues86 showed a significant association between tear film osmolality and age, along with changes in tear production and evaporation, which potentially could contribute to changes in osmolality.

Tear film osmolality in dry eye

According to Murube,54 recognition of the saltiness of tears with dry eye dates back to the second century AD. Mastman and colleagues87 were the first to measure higher salt concentrations in patients with dry eye but found this increase too small to contribute significantly to the disease. Since then, a variety of studies has been performed to establish the osmolality of the tear film in dry eye (Table 2). Agreement exists today that dry eye patients often present with tear film hyperosmolality.

Table 2. Summary of mean tear film osmolality findings in dry eye patients
Author and yearOsmometerMean osmolality in dry eye (mmol/kg)
  • † 

    Only units deviating from the usual one to express osmolality are displayed in the table, otherwise all measurements are summarised as mmol/kg.

  • ‡ 

    Tear film osmolality differences between women and men and between age groups.

  • § 

    Tear film osmolality differences between dry eye patients caused by lacrimal gland disease, meibomian gland dysfunction or a combination of both.

Mastman, Baldes and Henderson87 1961Baldes-Vapour pressure osmometer0.970 g/100 mg
Mishima114 1971Freezing point depression osmometer329 ± 4.7
Gilbard, Farris and Santamaria93 1978Freezing point depression osmometer343 ± 32.3
Gilbard and Farris111 1979Freezing point depression osmometer360 ± 74
Farris and colleagues115 1981Freezing point depression osmometer325 ± 8 to 337 ± 16
Farris and colleagues116 1983Freezing point depression osmometer326 ± 20
Gilbard and Kenyon117 1985Freezing point depression osmometer332 ± 3
Farris and colleagues85 1986Freezing point depression osmometer324 ± 11
Gilbard and colleagues113 1989Freezing point depression osmometer317 ± 2.4
Lucca and colleagues94 1990Freezing point depression osmometer323 ± 12
Gilbard118 1994Freezing point depression osmometer311.5 ± 1.1 to 317.2 ± 1.1§
Ogasawara and colleagues58 1996Conductivity324.8 ± 41 mEq/l
Mathers and colleagues119 1996Freezing point depression osmometer313 ± 9
Narayanan and colleagues120 2005Vapour pressure osmometer307.68 ± 13.86
Sullivan and colleagues59 2005‘Lab on a chip-osmometer’334
Srinivasan and colleagues121 2007Freezing point depression osmometer328.1 ± 20.8
Khanal and colleagues95 2008Freezing point depression osmometer328.71 ± 13.73

The diagnosis of dry eye is often complicated due to a lack of a clear correlation between symptoms and objective clinical signs, prompting many clinicians to evaluate dry eye on the premise of symptoms.88–92

The lack of a suitable single dry eye test and the persistence of tear film hyperosmolality in dry eye led to investigations of the measurement of tear film osmolality as a possible means of distinguishing dry eye from non-dry eye patients. As a single measurement test, using a cut-off value of 312 mmol/kg, determination of dry eye via tear film osmolality provided a sensitivity of 94.7 per cent and a specificity of 93.7 per cent.93 This result was confirmed by Lucca and colleagues94 and prompted Farris4 to propose tear film osmolality measurements as the new ‘gold standard’ in the evaluation of dry eye. At the 1995 NEI/Industry workshop, the measurement of tear film osmolality was incorporated as a global test for dry eye.5

Recent studies have suggested slightly higher cut-off values of 316 mmol/kg, obtained through a meta-analysis of published literature, and 317 mmol/kg, obtained through a clinical study.60,95 Overall accuracies for these cut-off values in identifying dry eyes were 89 and 79 per cent, respectively.60,95

A more detailed summary of the levels of tear film osmolality for the different classifications of dry eye was provided by Craig,41 who categorised normal eyes as having an expected range less than 312 mmol/kg, borderline dry eye between 312 and 323 mmol/kg and moderate to severe dry eye as more than 323 mmol/kg.

Tear film osmolality in contact lens wear

Osmolality of the tear film in contact lens wearers has attracted interest due to its possible role in the reduction of lens movement and increase in contact lens adherence. Additionally, the elevation of tear film osmolality due to the impact of contact lenses on tear film integrity has been investigated.

The insertion of contact lenses leads to an initial reduction in tear film osmolality, possibly caused by tear fluid hypersecretion due to irritation evoked by the contact lens.97–99 This decrease in tear film osmolality has been regarded as a contributor to post-lens tear film depletion with subsequent lens adherence and as a cause of increased corneal thickness during the adaptation phase to contact lenses.97,100

The initial decrease in tear film osmolality immediately after lens insertion is often followed by a shift towards hyperosmolality on equilibration of the contact lens.98,99,101 An inter-eye response has been demonstrated with changes in tear film osmolality not only being observable in the lens-wearing eye but also in the contralateral non-lens-wearing eye, although to a smaller extent.98,101

The elevation of tear film osmolality over time and the influence of wear modality or lens material on tear film osmolality seems to be controversial. Some studies have reported a return of tear film osmolality to its pre-insertion levels after 60 minutes or six days of lens wear.99,101 In contrast, other studies have shown that tear film osmolality remained elevated over 60 minutes98 or three months.102

Table 3 provides a summary of tear film osmolalities with different types of contact lens materials and lens-wear modalities. Farris103 showed that extended wear of soft contact lenses and daily wear of hard contact lenses had a significant effect on tear film osmolality but wear of soft contact lenses on a daily wear basis did not influence tear film osmolality. In contrast, Miller and colleagues104 demonstrated a significant increase in tear film osmolality with daily wear soft contact lenses. Studies investigating the effect of HEMA-based and silicone hydrogel contact lenses on tear film osmolality have been unable to demonstrate a significant difference between lens types.104,105

Table 3. Summary of tear film osmolality findings during contact lens wear
Author and yearOsmometerSubject groupTear osmolality (mmol/kg)
  • † 

    Although studies have used different osmometers and therefore different units, for simplification all units are considered as mmol/kg.

Nichols and Sinnott96 2006Freezing point depression osmometerContact lens-induced dry eye subjects307.66 ± 32.39
Non-dry eye contact lens wearers297.06 ± 31.38
Miller and colleagues104 2004Vapour pressure osmometerControl group305 ± 21
Hydrogel daily wear319 ± 30
Silicone hydrogel continuous wear319 ± 32
RGP324 ± 25
Iskeli and colleagues102 2002Freezing point depression osmometerHydrogel daily wear (55% H2O)312.15 ± 16.03
Hydrogel daily wear (38.6% H2O)316.54 ± 12.14
RGP (90 Dk)313.14 ± 9.66
RGP (52 Dk)316.38 ± 11.6
Dabney and colleagues105 2000Vapour pressure osmometerControl group309.0 ± 17.0
Hydrogel313.7 ± 28.5
Silicone hydrogel324.3 ± 41.7
RGP317.0 ± 13.0
Martin98 1987Freezing point depression osmometerBaseline316
Hydrogel lens eye331
Contralateral eye320–326
Farris103 1986Freezing point depression osmometerAphakic control321 ± 9
Aphakic extended wear318 ± 7
Phakic rigid lens daily wear316 ± 6
Phakic hydrogel lens daily wear309 ± 8
Phakic hydrogel lens extended wear318 ± 7
Stahl and colleagues122 2009Vapour pressure osmometerBaseline314.4 ± 13.9
Hydrogel323.1 ± 13.3
Silicone hydrogel321.5 ± 17.6
Glasson and colleagues123 2005Vapour pressure osmometerBaseline322.4 ± 16.7
Hydrogel318.1 ± 12.8

Most studies assessing tear film osmolality during contact lens wear required a high tear volume for the measurements, requiring collection of large tear volumes or tear dilution with consequent recalculation.102,104,105 Application of these sampling techniques might have potentially masked small differences between lens types, therefore acting as a mitigating factor, and might explain the often reported lack of differences in tear osmolality between lenses.

The importance of tear osmolality measurements in dry eye has prompted some limited research about osmolality levels in intolerant (symptomatic) contact lens wearers and has shown higher tear film osmolality in intolerant lens wearers with (307.66 ± 32.39)96 and without (324.4 ± 6.4)106 lens wear compared with tolerant (asymptomatic) wearers with (297.06 ± 31.82)96 or without (317.4 ± 8.9)106 lens wear measured with a freezing point depression or vapour pressure osmometer.

Tear film hyperosmolality

Tear film hyperosmolality results from increased evaporation of the tear film possibly coupled with reduced tear production.74,107 Tear film hyperosmolality is regarded as the core mechanism in dry eye and has been included in the definition of dry eye by the 2007 Dry Eye Workshop.2

As described earlier, work by King-Smith and colleagues35 suggests that the reported rates of evaporation significantly underestimate actual evaporation. Rapid tear thinning due to evaporation can lead to tear film instability, which in turn can cause local drying and substantial elevation in film osmolality across the ocular surface. This local rise would be considerably higher than that measured in the tear meniscus. These findings support the original hypothesis by Bron and colleagues,81 who considered that the osmolality across the ocular surface is higher than that measured in the tear meniscus.

King-Smith and colleagues35 proposed that a three-fold tear thinning could lead to a three-fold increase in tear osmolality and therefore tear hyperosmolality (300 to 900 mmol/kg). The link between tear film thinning, instability and tear hyperosmolality was recently demonstrated through investigation of the ocular symptoms during tear film break-up and the osmolality level required to create the same ocular symptoms during application of a solution.108 Solution osmolalities of 800 to 900 mmol/kg were required to evoke ocular discomfort in the form of burning and stinging, which suggests a transient peak in tear film osmolality during tear film break-up and supports the proposed shift in osmolality by King-Smith and colleagues.35

Tear film hyperosmolality stimulates inflammatory events involving mitogen-activated protein kinase and nuclear factor-kappa beta signalling pathways and the generation of inflammatory cytokines and metalloproteinases (MMP9).2,108–110 Elevated tear film osmolality negatively affects ocular surface cells and leads to pathological changes, such as a decrease in mucus-containing goblet cells, a decrease in intercellular connection, loss of microplicae and disruption of cell membranes.111–113 These changes increase tear film instability and tear film hyperosmolality leading to further exacerbation of dry eye symptoms and ocular surface changes.


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  2. Abstract

It is evident that an equilibrium in tear film production, retention and elimination is vital for the tear film to be able to fulfil its numerous roles and consequently for ocular surface health. Alterations to any component of the tear film dynamics will destabilise tear film homeostasis and lead to tear film instability and ocular surface changes. An imbalance in tear dynamics can be assessed via tear film osmolality. Tear film hyperosmolality is a key diagnostic feature in dry eye disease and there is some evidence to suggest that in symptomatic contact lens wearers, tear film osmolality is also increased. The measurement of tear film osmolality provides a useful clinical tool in the assessment of dry eye and for reduced tolerance to contact lens wear, particularly when clinical signs and ocular symptoms do not correlate. It also offers an excellent opportunity for deciding on management, particularly in view of the enhanced treatment options available. Subsequent monitoring can be improved through sequential tear film osmolality measurements by providing an early insight into the efficacy of the chosen treatment, that is, even when symptoms or other ocular signs might not have improved. The release of new osmometers that use tiny volumes of tears for measurement or allow direct osmolality measurements on the eye will simplify use and therefore encourage integration of this important measurement into routine clinical practice.


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  2. Abstract

This work was supported in part by the Australian Government through the Cooperative Research Centres Scheme, the International Postgraduate Research Scholarship through The University of New South Wales and the Contact Lens Society of Australia Research Award (US).


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