C L I N I C A L A N D E X P E R I M E N T A L
OPTOMETRY
cxo_634 3..11
Osmolality and tear film dynamics
Clin Exp Optom 2012; 95: 1: 3–11
Ulrike Stahl*† PhD
Mark Willcox*†§ PhD
Fiona Stapleton*†§ PhD
* Vision Cooperative Research Centre,
Sydney, Australia
†
School of Optometry and Vision
Sciences, University of New South Wales,
Sydney, Australia
§
Institute for Eye Research, Sydney,
Australia
E-mail: u.stahl@unsw.edu.au
Submitted: 2 February 2010
Revised: 16 December 2010
Accepted for publication: 1 May 2011
Key words: dry eye, osmolality of tears, tears
The pre-ocular tear film is the outermost
layer of the eye and is of critical impor-
tance to the health of the ocular surface. A
continuous cycle of production, evapora-
tion, absorption and drainage leads to a
dynamic equilibrium in the pre-ocular
tear film. Tear film osmolality or tear salti-
ness can be considered a consequence of
these various factors in tear film dynam-
ics.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
© 2011 Vision Co-operative Research Centre
Clinical and Experimental Optometry © 2011 Optometrists Association Australia
REVIEW
DOI:10.1111/j.1444-0938.2011.00634.x
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.
composition, ultimately leading to tear edge of tear film dynamics and the rel-
film instability and tear film hyperosmola- evance and clinical implications of tear
lity.2 Measurement of tear film osmolality film osmolality.
has been suggested as a gold standard in
the diagnosis of dry eyes as elevated tear
TEAR FILM STRUCTURE AND
film osmolality is considered a core
FUNCTION
mechanism in symptoms and ocular
surface damage in dry eye.2,4,5 The classical description of the tear film is
Despite its immense potential in the a three-layered structure, with a predomi-
diagnosis of dry eye, measurement of tear nant aqueous phase, a superficial thin oily
film osmolality has not been amenable to layer, which interfaces with the environ-
in-office use and is largely confined to use ment, and a deep mucous layer at the
in research. Newly available technology base.6,7 The thickness of the tear film was
might increase its uptake by clinicians. originally estimated to be 4 to 8 mm, with
This review focuses on the current knowl- the aqueous layer being the thickest
Clinical and Experimental Optometry 95.1 January 2012
3
Osmolality and tear film dynamics Stahl, Willcox and Stapleton
layer (7 mm) and the lipid and mucous
layers each relatively thin at 0.1 and
0.05 mm, respectively.6,8,9 Using non-
invasive laser interferometry and confocal
microscopy, Prydal and colleagues10 mea-
sured a tear film thickness of approxi-
mately 40 mm and attributed this new
thickness to previous underestimations of
the mucin layer. These thickness measure-
ments 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 con-
centration 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 mm.
The mucous layer, produced by the
goblet cells and corneal and conjunctival
epithelia, is composed of secreted and
transmembrane mucins, immunoglobu-
lins, salts, urea, enzymes, glucose and leu-
kocytes.13,14 Transmembrane mucins form
a dense hydrophilic barrier, protecting
the ocular surface against adherence of
pathogens and debris and increasing sta-
bility of the overlying tear film through
increased wettability. These mucins con-
tribute 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 lacri-
mal gland and by the accessory lacrimal
glands of Krause and Wolfring, the
aqueous layer consists of water, electro-
lytes, 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
Clinical and Experimental Optometry 95.1 January 2012
4 Clinical and Experimental Optometry © 2011 Optometrists Association Australia
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 sph-
ingolipids 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 func-
tions of the lipid layer are to provide a
smooth optical surface, to limit contamina-
tion of the eye from particles and organ-
isms 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
TEAR FILM DYNAMICS
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 stimula-
tion 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 environ-
ment and thus is subject to evaporation.
Similar to their effects on an exposed
water surface, environmental factors such
as humidity, temperature and air move-
ment 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 inter-
ferometry 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 measure-
ments support the results obtained by
interferometry.30,37 Higher evaporation
rates would have considerable impact on
tear film dynamics, stability and osmolal-
ity, 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, inflam-
matory 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 nega-
tive 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
© 2011 Vision Co-operative Research Centre

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 mecha-
nism 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 elimina-
tion via drainage in the model of tear
dynamics.
Tear absorption
Contributing to tear film dynamics, tear
film absorption occurs via the cornea, con-
junctiva and epithelium of the nasolacri-
mal 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
TEAR FILM OSMOLALITY
Definition of osmolality
Osmolality is defined as the total number
of dissolved solute particles in one kilo-
gram 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 osmo-
lality 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 osmo-
lality it is temperature dependent.53 Addi-
tionally, the volume of the solute particles
in a solution will create a difference
between osmolality and osmolarity, result-
ing in a higher osmolality than osmolarity.
This difference increases with more con-
centrated solutions; however, while this is
of importance for some body fluids, such
as blood plasma, the protein content in
© 2011 Vision Co-operative Research Centre
Clinical and Experimental Optometry © 2011 Optometrists Association Australia
Osmolality and tear film dynamics Stahl, Willcox and Stapleton
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 experi-
mentally and must be calculated, in
contrast to osmolality, which can be deter-
mined experimentally using available
osmometers.53 Calculations of osmolality
and osmolarity are not always straightfor-
ward. 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 col-
ligative properties of a solution, that is,
freezing point, boiling point, vapour pres-
sure 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 pres-
sure will decrease, while the boiling point
and osmotic pressure will increase. A rela-
tionship between the solvent chemical
potential and the colligative properties
forms the basis for osmolality measure-
ments of tears and other solutions.55
Although osmolality measurements via
boiling point or osmotic pressure are theo-
retically possible, limitations in suitable
membranes and solution instability at
high temperatures limit these applica-
tions. Therefore, traditionally, the osmola-
lity 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 addi-
tion of solute to the solvent. To determine
the osmolality of a solution, the sample
is supercooled (significantly below its
expected freezing point). During the crys-
tallisation process, heat of fusion is
released and the solution reaches a
plateau in temperature for a moment.
This temperature is measured and trans-
Clinical and Experimental Optometry 95.1 January 2012
lated into the corresponding osmolality of
the solution. Due to the measurement
technique used, freezing point osmom-
eters are not suitable for highly viscous
solutions. Additionally, the correlation
between freezing point depression and
osmolality is complex, resulting in a pos-
sible departure of the measured osmolal-
ity from the actual one. Particularly for
highly concentrated solutions, deviations
between actual and measured osmolality
can occur due to mathematical simplifica-
tions 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 ther-
mocouple 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 thermo-
couple reaches the dew point temperature
and the difference to the original refer-
ence temperature serves for the calcula-
tion of the solution’s osmolality. Although
osmolality measurements using vapour
pressure osmometry are often regarded as
ideal, there are limitations to this tech-
nique. Accurate measurements of solu-
tions 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 mea-
surements with a freezing point depres-
sion 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 mea-
5
Osmolality and tear film dynamics Stahl, Willcox and Stapleton
Concentration in mmol/kg
Na+ K+ Ca2+ Mg2+ Zn2+
120–170 6–42 0.3–2.0 0.3–1.1 50–100
Table 1. Main concentration of electrolytes in the tear film
surements with a freezing point depres-
sion 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, par-
ticularly for highly concentrated and very
complex solutions, currently these instru-
ments are used mainly for the determina-
tion 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, evapo-
ration, drainage and absorption.1 Mea-
surements 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 pro-
teins and sugars approximates 2.0 mmHg
and therefore is less than one per cent of
the total tear film osmolality.62 Of the elec-
trolytes 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).
Clinical and Experimental Optometry 95.1 January 2012
6 Clinical and Experimental Optometry © 2011 Optometrists Association Australia
mmol/kg mmol/kg
Mn2+ Cl- HCO3- PO43-
0.2–0.9 106–135 26 0.07
The main lacrimal gland, the accessory
lacrimal glands of Krause and Wolfring,
the cornea and the conjunctiva are
responsible for the secretion of electro-
lytes 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 capac-
ity 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 Secre-
tion from the main lacrimal gland is
stimulated by three different cellular
signal transduction pathways, which
stimulate a release and activation of pro-
teins 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 secre-
tion of tears by the conjunctival epithe-
lium remains unknown.68 In addition to
the secretion of water and electrolytes,
transport of water through the conjunc-
tiva 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 demon-
strated a constant flow of sodium and
chloride between 2 and 30 ml/min, but an
increase in concentration if the flow rate
was less than 0.5 ml/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 ml/min, but other-
wise it is independent of the flow rate.73
Gilbard and Dartt74 investigated the osmo-
lality 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 measure-
ments, 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 osmolal-
ity during the day.77–80 The osmolality of
tears sampled from the inferior tear
meniscus might underestimate the osmo-
lality of the tear fluid across the cornea
due to the variable effects of evapora-
tion.81 Benjamin and Hill82,83 were able to
demonstrate differences in osmolality
among ocular sites and between the infe-
rior tear meniscus and the cul-de-sac.
Although small differences in tear film
osmolality have been observed between
men and women, there is general agree-
ment 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 sig-
nificant 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
© 2011 Vision Co-operative Research Centre

Author and year
Mastman, Baldes and Henderson87 1961
Mishima 114
1971
Gilbard, Farris and Santamaria93 1978
Gilbard and Farris111 1979
Farris and colleagues115 1981
Farris and colleagues 116
1983
Gilbard and Kenyon117 1985
Farris and colleagues85 1986
Gilbard and colleagues113 1989
94
Lucca and colleagues 1990
Gilbard118 1994
Ogasawara and colleagues 1996 58
Mathers and colleagues119 1996
Narayanan and colleagues120 2005
Sullivan and colleagues59 2005
Srinivasan and colleagues121 2007
Khanal and colleagues95 2008
† 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.
Table 2. Summary of mean tear film osmolality findings in dry eye patients
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.
The diagnosis of dry eye is often compli-
cated 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 hyperos-
molality 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 mea-
surement test, using a cut-off value of
© 2011 Vision Co-operative Research Centre
Clinical and Experimental Optometry © 2011 Optometrists Association Australia
Osmolality and tear film dynamics Stahl, Willcox and Stapleton
Osmometer
Baldes-Vapour pressure osmometer
Freezing point depression osmometer
Freezing point depression osmometer
Freezing point depression osmometer
Freezing point depression osmometer
Freezing point depression osmometer
Freezing point depression osmometer
Freezing point depression osmometer
Freezing point depression osmometer
Freezing point depression osmometer
Freezing point depression osmometer
Conductivity
Freezing point depression osmometer
Vapour pressure osmometer
‘Lab on a chip-osmometer’
Freezing point depression osmometer
Freezing point depression osmometer
312 mmol/kg, determination of dry eye
via tear film osmolality provided a sensitiv-
ity 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 measure-
ment of tear film osmolality was incorpo-
rated 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
Clinical and Experimental Optometry 95.1 January 2012
Mean osmolality in dry eye (mmol/kg)†
0.970 g/100 mg
329 ⫾ 4.7
343 ⫾ 32.3
360 ⫾ 74
325 ⫾ 8 to 337 ⫾ 16‡
326 ⫾ 20
332 ⫾ 3
324 ⫾ 11
317 ⫾ 2.4
323 ⫾ 12
311.5 ⫾ 1.1 to 317.2 ⫾ 1.1§
324.8 ⫾ 41 mEq/l
313 ⫾ 9
307.68 ⫾ 13.86
334
328.1 ⫾ 20.8
328.71 ⫾ 13.73
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 hypersecre-
tion due to irritation evoked by the
contact lens.97–99 This decrease in tear film
osmolality has been regarded as a con-
tributor to post-lens tear film depletion
with subsequent lens adherence and as a
cause of increased corneal thickness
7
Osmolality and tear film dynamics Stahl, Willcox and Stapleton

Author and year Osmometer Subject group Tear osmolality (mmol/kg)†

Nichols and Sinnott96 2006 Freezing point depression osmometer Contact lens-induced dry eye subjects 307.66 ⫾ 32.39
Non-dry eye contact lens wearers 297.06 ⫾ 31.38
Miller and colleagues104 2004 Vapour pressure osmometer Control group 305 ⫾ 21
Hydrogel daily wear 319 ⫾ 30
Silicone hydrogel continuous wear 319 ⫾ 32
RGP 324 ⫾ 25
Iskeli and colleagues102 2002 Freezing point depression osmometer Hydrogel 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 2000 Vapour pressure osmometer Control group 309.0 ⫾ 17.0
Hydrogel 313.7 ⫾ 28.5
Silicone hydrogel 324.3 ⫾ 41.7
RGP 317.0 ⫾ 13.0
Martin98 1987 Freezing point depression osmometer Baseline 316
Hydrogel lens eye 331
Contralateral eye 320–326
Farris103 1986 Freezing point depression osmometer Aphakic control 321 ⫾ 9
Aphakic extended wear 318 ⫾ 7
Phakic rigid lens daily wear 316 ⫾ 6
Phakic hydrogel lens daily wear 309 ⫾ 8
Phakic hydrogel lens extended wear 318 ⫾ 7
Stahl and colleagues122 2009 Vapour pressure osmometer Baseline 314.4 ⫾ 13.9
Hydrogel 323.1 ⫾ 13.3
Silicone hydrogel 321.5 ⫾ 17.6
Glasson and colleagues123 2005 Vapour pressure osmometer Baseline 322.4 ⫾ 16.7
Hydrogel 318.1 ⫾ 12.8

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

Table 3. Summary of tear film osmolality findings during contact lens wear

during the adaptation phase to contact
lenses.97,100
The initial decrease in tear film osmola-
lity immediately after lens insertion is
often followed by a shift towards hyperos-
molality 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 con-
tralateral 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
Most studies assessing tear film osmola-
lity during contact lens wear required a
high tear volume for the measurements,
requiring collection of large tear volumes
or tear dilution with consequent recalcu-
lation.102,104,105 Application of these sam-

Clinical and Experimental Optometry 95.1 January 2012 © 2011 Vision Co-operative Research Centre
8 Clinical and Experimental Optometry © 2011 Optometrists Association Australia

pling 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 osmo-
lality between lenses.
The importance of tear osmolality mea-
surements 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 pos-
sibly coupled with reduced tear produc-
tion.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 eleva-
tion in film osmolality across the ocular
surface. This local rise would be consider-
ably higher than that measured in the tear
meniscus. These findings support the
original hypothesis by Bron and col-
leagues,81 who considered that the osmo-
lality 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 hyperosmo-
lality was recently demonstrated through
investigation of the ocular symptoms
during tear film break-up and the osmola-
lity level required to create the same
ocular symptoms during application of a
© 2011 Vision Co-operative Research Centre
Clinical and Experimental Optometry © 2011 Optometrists Association Australia
Osmolality and tear film dynamics Stahl, Willcox and Stapleton
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 hyperos-
molality leading to further exacerbation of
dry eye symptoms and ocular surface
changes.
CONCLUSION
It is evident that an equilibrium in tear
film production, retention and elimina-
tion 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 mea-
surement 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
Clinical and Experimental Optometry 95.1 January 2012
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 measure-
ment or allow direct osmolality measure-
ments on the eye will simplify use and
therefore encourage integration of this
important measurement into routine
clinical practice.
GRANTS AND FINANCIAL ASSISTANCE
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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