Review

Evaporation from the ocular surface

William Mathers*

Casey Eye Institute, Oregon Health and Sciences University, 3375 SW Terwilliger, Portland, OR 97201, USA

Received 19 June 2003; accepted 20 June 2003

Abstract

Evaporation from the ocular surface is dramatically reduced by the lipid layer which covers it. With this layer intact, evaporation

represents a small loss of water for which the lacrimal gland easily compensates. When tear production is compromised evaporation becomes

important, especially since evaporation in almost all ocular surface disease states and any surface perturbation, including contact lens wear,

increases evaporation significantly.

How the barrier function of the lipid layer accomplishes this reduction in evaporation is not understood and is probably quite complex as is

the structure of the lipid layer. Improving this barrier function remains an important and elusive goal.

q 2003 Elsevier Ltd. All rights reserved.

Keywords: evaporation; lipid layer; dry eye; meibomian gland; lacrimal gland

1. Introduction

The tear film is the primary interface between the ocular

system and the visual world, and determines much of the

accuracy of the optical system. A primary reason for

studying the tear film is to maintain this optical function. In

addition, deficient wetting of the ocular surface and dry eye

syndrome present a major source of morbidity for a sizable

portion of the population. Nearly half of women between the

ages of 35 and 60 complain of occasional dry eye

symptoms, and 10–15% of the older adult population

have frank dry eye (McMonnies and Ho, 1987; Bjerrum,

1997; Schein et al., 1997; Caffery et al., 1998; McCarty

et al., 1998; Mathers et al., 2002; Schaumberg et al., 2000).

The tear film is a dynamic system, consisting of tear

production washing over the epithelial and conjunctival

cells, tear drainage through the lacrimal duct, fluid

absorbtion or exchange through the conjunctival and

corneal epithelium, and water evaporating to the air. It is

in a constant state of flux, continuously thinning when the

eye is open, and refreshed with blinking. Evaporation is part

of this equation.

2. Description of the evaporative process

Evaporation from a liquid into a gas from a surface is

determined by the vapor pressure of that fluid, which varies

with temperature. This description is deceptively simple.

There is a differential in vapor pressure between the

immediate surface and more distant gas, which is altered

by air currents, and there is temperature differential between

the water surface and deeper layers of the liquid. In addition,

the purity of the solution affects vapor pressure. These

factors were discussed by Hickman and Torpey (1954), who

set out a series of equations and described an apparatus to

evaluate evaporation of resting water. Approximate equiv-

alence of measurement and theory was achieved by this

study. Gilbert and Tator (1971) presented additional

refinements to these equations for organic solvents. The

temperature differential within the water was further

investigated by Bertrand in 1979 and by Kaplon in1986

Kaplon et al., 1986. Information, helpful in assessing

evaporation from the ocular surface, was first published by

Hisatake in 1993 Hisatake et al., 1993. Their charts of

evaporation as a function of temperature, humidity, and air

velocity, demonstrate evaporation would be approximately

170 £ 1027 ml min21 at 30% humidity and 348.

0014-4835/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.

DOI:10.1016/S0014-4835(03)00199-4

Experimental Eye Research 78 (2004) 389–394

www.elsevier.com/locate/yexer

* Address: Casey Eye Institute, Oregon Health and Sciences University,

3375 SW Terwilliger, Portland, OR 97201, USA.

E-mail address: mathersw@ohsu.edu (W. Mathers).

3. The role of monolayers in evaporation

The ocular surface is covered with a thin layer of lipid,

which functions like a monolayer to retard evaporation. An

excellent discussion of monolayer function was presented in

1954 by Archer, which included a description of an

apparatus and measurements of the specific resistance of

three long-chain fatty acids (Archer and LaMer, 1954). In

1955, Rosano published results of experiments with

monolayer retardation of evaporation as a function of

monolayer surface pressure and compressibility (Rosano

and LaMer, 1956). LaMer, in 1959, found that impurities

alter monolayer resistance (LaMer and Barnes, 1959). This

is highly relevant since the ocular monolayer is very

complex and composed of lipids, proteins, and multiple

ions, easily subject to contamination. In addition, the action

of the eyelid stretches and compresses the lipid layer, further

altering its properties as occurs in other monolayers

(Cammenga and Koenemann, 1987).

The structure of the lipid layer and thus its anti-

evaporative mechanisms remains poorly understood. A

bipolar inner layer mostly likely interdigitates and acts as a

transition zone between the outside nonpolar surface and the

polar aqueous tear film. Phosphatidyl ethanolamines,

sphingomyelin, and phosphatidyl choline are probably key

components of this polar lipid layer. A description of how

polar lipids organize and create the extremely highly

effective nature of the lipid barrier was presented by

McCulley in 2000 (McCulley and Shine, 2000). The

evaporative surface is highly effective, dramatically demon-

strated by the 95% reduction in evaporation from the ocular

surface. The most successful simple monolayers yet

developed only retard evaporation 60–70% (Mathers and

Lane, 1998).

4. Evaporation models and examples

Clinical experience has shown that evaporation rates

differ between animals and between groups of human

subjects. It is well known that rabbits have a very stable tear

film and a very low blink rate, which has led most

investigators to assume that their ocular evaporation must

be very low (Maurice, 1995). Human infants blink less than

adults, often only 3–4 times a minute, and their tear film

appears to be unusually stable, compared with adult

humans. This strongly suggests they have a tear film that

protects against evaporation to a higher degree than adults

have.

5. The measurement of evaporation and the development

of devices

The first measurement of evaporation was made by

von Bahr (1941) with a chamber fixed around a rabbit

cornea (Table 1). He found an evaporative rate of 41·6 £

1027 g cm22 sec21. Mishima and Maurice (1961) measured

corneal thickness in rabbit eyes whose anterior chamber was

filled with oil and determined the evaporative rate to be 7·8

using the same units. They also established that the lipid

layer retarded evaporation. Iwata and Dohlman, developed

another vitro rabbit model, using a cornea covered with a

chamber over which passed dry air. The weight of water

Table 1

Summary of evaporation studies

Year Investigator Animal Normal subj RH% Dry eye subj Ocular dis Obst. MGD MGD þ DE

1941 Von Bahr Rabbit 41·6

1961 Mishima Rabbit 7·8

1969 Iwata Rabbit 10·1

1980 Hamano Rabbit 11·4

1980 Hamano Human 26·9 15·2

1983 Rolando Human 4·07 8·03

1990 Yamada Human 32·4 40% 16·5

1991 Tomlinsona Human 20 35

1992 Tsubota Human 15·6 40% 9·5

1993 Mathers Human 14·7 30% 47·6

1993 Mathers Human 14·8 30% 49·9 59

1995 Shimazaki Human 15·6a 40% 18·4

1995 Shimazaki Human 15·6a 40% 12·5 20

1996 Mathers Human 13 30% 25

1996 Mathers Human 15·1 30%

1997 Craiga Human 1·42 50% @ 258 5·9

2000 Craiga Human 0·07 50% @ 258 1·48

2003 Goto Human 4·1 5·8

Normal subj: normal subject, RH%: relative humidity, Dry eye subj: dry eye subjects, Ocular dis: ocular surface disease, Obst MGD: obstructive

meibomian gland disease, MGD þ DE: Meibomian gland disease and dry eye.a Units ¼ g m22 hr21, All values are in units £ 1027g cm22 sec21 except those with asterisk.

W. Mathers / Experimental Eye Research 78 (2004) 389–394390

collected determined the evaporative rate, which they

calculated to be 10·1 £ 1027 g cm22 sec21 (Iwata et al.,

1969). This is remarkably close to subsequent values that

were achieved in other in vivo systems. They also

established that both the lipid layer and the epithelium

were effective barriers. With the epithelium removed, a 20-

fold increase in evaporation was seen, compared with a 4-

fold increase that occurred after the removal of the lipid

layer.

Hamano was first to measure in vivo evaporation in the

human in 1980 (Hamano et al., 1980). He found an

evaporation rate 26·9 £ 1027 g cm22 sec21. Rolando and

Refojo (1983) reported a device to measure tear evaporation

in the human eye in vivo that consisted of a modified tight

fitting goggle, with dry air pumped into its chamber. After

1 min of evaporation, the air in the chamber was mixed with

the air in the system and measured for temperature and

humidity. The air temperature of this system was 238C.

They found an evaporation rate for normal eyes of

4·07 £ 1027 g cm22 sec21 in normal eyes. This type of

device could not evaluate evaporation at a precise

temperature or relative humidity. To minimize the contri-

bution of skin evaporation they covered the exposed area

with petroleum jelly. They established the concept of

evaporation as a function of the interpalpebral fissure, and

created a chart describing the relationship between exposed

area and interpalpebral distance in mm.

Yamada and Tsubota (1990) described a device in a

Japanese publication that also used a chamber filled with dry

air that was sealed and the relative humidity measured over

time. The differential evaporation rate could thus be

determined for any arbitrary humidity. They reported

normal evaporation was 15·6 £ 1027 g cm22 sec21 at 40%

relative humidity. Their English language paper followed in

1992 with similar results (Tsubota and Yamada, 1992).

They also reported that the insertion of lacrimal collagen

plugs to occlude the inferior puncta increased evaporation

rate, and that artificial tear eye drops also increased

evaporation. Tomlinson et al. (1991) reported the develop-

ment of a device they tested on three patients but failed to

find a correlation between tear flow and evaporation rate. He

also found that preservatives in artificial tears increased the

evaporation rate (Tomlinson and Trees, 1991).

The author reported the development of a device for

measuring evaporation in 1993 (Mathers et al., 1993). Using

a small closed chamber filled with dry air, the rise in

humidity was plotted and evaporation calculated. Evapor-

ation rate of the closed eye was subtracted to remove the

affect of evaporation from the skin. Petroleum jelly was not

used since it increased evaporation measured from the skin,

however, to avoid error from skin loss, subjects were

tested in a cool room with dim light and at a state of

rest. They found normal evaporation to be 14·7 ^ 6·4 £

1027 g cm22 sec21 at 30% relative humidity.

The most recent report on evaporation rate was by Goto

and Tsubota in 2003 (Goto et al., 2003). They used a device

that streamed air of know humidity across the ocular surface

and subtracted the evaporation effect from the closed eye.

With this instrument the rate in normal subjects was

much lower than had previously been found, 4·1 þ 1·4 £

1027 g cm22 sec21. The relative humidity of the incoming

air, not reported for this result, was factored out of the final

equation and their results may not be directly comparable to

other reports.

6. Evaporation and dry eye

The primary impetus to study evaporation from the

human eye was to improve our understanding of dry eye. As

shown above, the evaporation rate of a pure water surface is

very high, 170 ml min21 at 34 8C, a rate that would quickly

lead to dry eye. The early studies by Iwata confirmed the

lipid barrier was important in reducing evaporation, and that

the epithelium presented a significant barrier as well (Iwata

et al., 1969). Hamano’s early experiments suggested that

evaporation in dry eye subjects was actually lower than in

normal subjects, however, Rolando’s results in patients with

dry eye or mixed ocular surface pathology, found

evaporation rates were double the normal rate (Hamano

et al., 1980; Rolando et al., 1983). Seven years later,

Yamada and Tsubota found evaporation in dry eye was

again lower than normal although the same group published

an addition study in 1995 that found the dry eye rate, 12·5, to

be nearly the same as the normal, 15·1 (Yamada and

Tsubota, 1990).

The author’s first studies, published in 1993, followed

the development of their own device and showed

dry eye subjects had quite high evaporative rate, 47·6 £

1027 g cm22 sec21, compared with a normal rate of 14·7

(Mathers, 1993). All of these dry eye subjects had low tear

production with low Schirmers tests. This result was

confirmed with additional studies published in 1996 that

found a rate of 25 £ 1027 g cm22 sec21 in the dry eye

compared to a normal control of 13 (Mathers and Daley,

1996). In 2000 Craig and Tomlinson examined nine patients

with dry eye and 13 healthy control subjects, and found

evaporation rate was much higher in dry eye, with higher

tear osmolarity, and higher temperature variation measured

by infrared imaging of the ocular surface (Craig et al.,

2000). This clarified the relationship between evaporation

and ocular surface temperature, and supported an increased

evaporation rate in dry eye. These reports used g/m2/hr at

258 and 50% relative humidity and a measuring device

based on steady state differential humidity within a

chamber.

If evaporation is clinically relevant to dry eye, it requires

evaporation to be a meaningful percentage of tear flow.

Early measurements of tear flow based on fluorophotometry

or other devices suggested a rate of 0·9–1·2 ml min21 for

the normal tear film, and evaporation rates of 10–40 £

1027 g cm22 sec21 which translates to an average tear

W. Mathers / Experimental Eye Research 78 (2004) 389–394 391

evaporation loss of 0·1–0·4 ml min21 (Mishima et al., 1966;

Tsubota and Yamada, 1992; Jordan, 1980; Brubaker et al.,

1990). Evaporation would only be 10% of the total tear

production in this case. The authors’ fluorophotometric

measurements of tear flow have found the early estimates of

tear flow to have been overestimated and that normal tear

flow averages 0·36 ml min21 in the un-stimulated eye

(Mathers et al., 2002). Our current estimate for normal

evaporation is 15 £ 1027 g cm22 sec21 or 0·15 ml min21

(Mathers and Daley, 1996). Thus, evaporation in the

normal, un-stimulated eye represents 36% of a combined

total of 0·41 ml min21. The normal lacrimal gland has a

great deal of reserve capacity and can easily compensate for

any brief increase in evaporation. For dry eye subjects, our

average flow measured 0·18 ml min21 and evaporation was

0·25 ml min21. In this comparison the total combined flow

is nearly the same for normals and dry eye subjects,

0·43 ml min21, but the percentage loss from evaporation is

higher in dry eye (55%). In dry eye subjects there is little

reserve capacity to compensate for any increased evapor-

ation. In more severe dry eye subjects, all tear production

must be lost to evaporation or is absorbed trans-conjunctiv-

ally since total punctual occlusion rarely produces frank

epiphora.

7. Meibomian gland function and evaporation

The effect of meibomian lipids on evaporation rate may

be even greater than the effect of dry eye since meibomian

gland dysfunction appears to alter the lipid layer and hinders

its evaporative control. The protective effect of the lipid

layer was described in 1961 by Mishima (Mishima and

Maurice, 1961). He did not, however, report on the actual

measurement of evaporation in this early discussion. In

1983, Rolando reported an increase in evaporation in

patients with ocular surface disease, some of whom had

meibomian gland dysfunction (Rolando et al., 1983) (Table

1). Tiffany (1985) reviewed what was then known about

evaporative function and meibomian gland disease.

In 1993, the author presented data demonstrating

meibomian gland dysfunction altered evaporation rate,

which correlated closely with gland dropout (Mathers,

1993). The highest rates of evaporation were found in

patients with both dry eye and meibomian gland dropout.

This was confirmed in 1995 by a paper published in Japan

by Shimazaki who also found increased evaporation in

patients with meibomian gland dropout (Shimazaki et al.,

1995). The relationship between evaporation and quantifi-

able tear parameters versus meibomian gland function,

measured by expressed lipid volume, viscosity, and gland

dropout, was presented as part of a model of tear function by

the author in 1996 (Mathers et al., 1996). The correlation

between these tear parameters and evaporation was

evaluated in a group of 156 patients. The strongest

correlation was found between osmolarity and evaporation,

and between lipid volume and evaporation in a group of

widely divergent subjects. The next year, Craig and

Tomlinson (1997) found evaporation was increased in

subjects with a thin lipid layer and in subjects with abnormal

interference patterns indicating meibomian gland dysfunc-

tion. A recent paper by Goto confirmed that patients with

obstructive meibomian gland dysfunction have elevated

evaporation rates (Goto et al., 2003).

In summary, evaporation has generally been found to

increase in patients with dry eye and with meibomian gland

dysfunction. Some of the inconsistencies in the above

studies, particularly regarding evaporation in dry eye, may

have more to do with subject selection than with physiology,

measurement techniques, and instrumentation. Normal

versus dry eye is not an exact diagnosis and inclusion

criteria rarely are precise enough to select subjects with pure

low flow dry eye or with pure obstructive meibomian gland

dysfunction without dry eye. This may be clarified by our

cluster analysis of 516 subjects with various combinations

of dry eye, seborrheic, and obstructive meibomian gland

dysfunction, and normal subjects recently submitted for

publication. This analysis was complex but, in summary, we

drew several conclusions. Meibomian gland dropout was

strongly associated with increased evaporation. Seborrheic

meibomian gland dysfunction without dry eye had low

evaporation but with dry eye it was elevated. Most subjects

with low Schirmers had increased evaporation but there

were subjects with low Schirmers and normal evaporation

rates. There is also a segment of the normal population that

has a high rate of evaporation without dry eye or meibomian

gland disease. When dry eye disturbs the ocular surface it

appears to alter the integrity of the lipid layer in some way

that raises evaporation. In obstructive meibomian gland

disease the lipid layer is also compromised. The cause of

this is not known. The thicker lipid layer found in seborrheic

meibomian gland dysfunction appears to be protective but

this too may not be completely effective.

8. Contact lenses and evaporation

Wearing a contact lens also increases evaporation.

Hamano estimated evaporation from a human eye wearing

a contact lens in 1981, and Tomlinson examined this issue in

1983 (Hamano, 1981; Cedarstaff and Tomlinson, 1983).

They both found contact lenses increased evaporation.

Tomlinson found the increase was not consistently related to

the water content of the lens. Water loss by dehydration of

the lens made only a minor contribution to the total increase

in evaporation.

The author studied evaporation in 10 subjects wearing

various types contact lenses and found evaporation

increased with old lenses but not with a new lens recently

placed on the eye. For that study, subjects were first tested

for evaporation and tear osmolarity wearing their old lens.

The following day they were tested again before wearing

W. Mathers / Experimental Eye Research 78 (2004) 389–394392

a contact lens and then after wearing a new lens for a few

minutes. Evaporation with the new lens was the same as

without the lens and consistently lower than with the old

lens. Tear osmolarity changed in a corresponding manner

with these results (Table 2). The results were consistent and

seen with all types of lenses.

9. Therapeutic measures to control dry eye

Measures to decrease evaporation in an effort to

alleviated dry eye have pursued several avenues including

additives to improve lipid barrier function, measures to

improve ocular surface health, and physical aids to increase

humidity around the eye. Evaporation is most likely a

function of many interacting variables and an improvement

in one or more of these may or may not lower evaporation.

In dry eye, epithelial cells desquamate at an accelerated rate

and treating the eye with frequent applications of an

appropriate artificial tear has been shown to decrease the

desquamation rate as the eye returns toward a state of health

(Gilbard, 1996). The evaporation rate probably improves as

well since homeostasis is restored and the mucin layer

becomes healthier and stabilizes the tear film. This is

speculative since it has not been measured.

Toda found evaporation rate was increased for 30 min

after 0·5% hydroxypropyl methylcellulose was applied but

there was no increase when only 0·1% solution was used

(Toda et al., 1996). This is in keeping with the experience of

the author who has tested many agents, artificial tears,

ointments and lipids including the surfactant phospholipids

used to stabilize alveolae. All of these increased evapor-

ation. This does not mean that the addition of some agent or

combination of agents could not be found to achieve this

goal. The lipid layer and its interaction with the aqueous and

mucin components is very complicated and it may require

the right mixture to improve. Other combinations probably

disrupt the lipid layers complex structure and work against

this end. Tsubota may have succeeded in lowering

evaporation by applying a calcium-based ointment to the

skin of the lower lid (Tsubota et al., 1999). As the petroleum

based ointment spread over the skin and then to the surface

of the eye, it improved symptoms of dry eye and also

lowered evaporation. This has not been independently

confirmed but it is very encouraging result. Korb described,

in a 2001 abstract, the application of several phospholipids

and found anionic phospholipids in non-polar oil increased

the thickness of the lipid layer whereas zwitterionic neutral

phospholipids did not. Evaporation was not measured (Korb

et al., 2001).

Moisture chamber prosthetic devices coupled to eye-

glasses can also decrease evaporation if sufficient humidity

can be maintained around the eye (Hart et al., 1994). Many

patients with severe dry eye find these help their symptoms.

Evaporation rate cannot be simultaneously measured while

the device is worn but the logic is compelling that

evaporation would be reduced as humidity increases.

10. Conclusions

Evaporation from the ocular surface is dramatically

reduced by the lipid layer covering it. With this layer

intact, evaporation represents a small loss of water for

which the lacrimal gland easily compensates. When tear

production is compromised evaporation becomes import-

ant, especially since evaporation in almost all ocular

surface disease states and any surface perturbation,

including contact lens wear, increases evaporation signifi-

cantly. How the barrier function of the lipid layer

accomplishes this reduction in evaporation is not under-

stood and is probably quite complex as is the structure of

the lipid layer. Improving this barrier function remains an

important and elusive goal.

Acknowledgements

Supported in part by a grant from NIH- RO1 EY10164

and RPB Inc.

References

Archer, R.J., LaMer, V.K., 1954. The effect of monolayers on the rate of

evaporation of water. Ann. N.Y. Acad. Sci. 58, 807–829.

von Bahr, G., 1941. Konnte der Flussigkeitsabgang durch die Cornea von

physiologischer Bedeutung sein? Acta Ophthalmol. 19, 125–134.

Bjerrum, K.B., 1997. Keratoconjunctivitis sicca and primary Sjogren’s

syndrome in a Danish population aged 30–60 years. Acta Ophthalmol.

Scand. 75, 281–286.

Table 2

Evaporation in contact lens subjects

Evaporation Osmolarity

Lens type n Old lens No lens New lens Old lens No lens New lens

DW worn for 6 weeks 4 23·0 þ 11·8 10·8 þ 0·9 14·8 þ 3·0 309 þ 8 301 þ 1 306 þ 7

DW worn for 1 week 4 33·4 þ 12·2 25·5 þ 20·0 22·4 þ 12·6 316 þ 6 308 þ 9 309 þ 6

RGP 1 28·9 17·6 13·2 309 300 307

Single Use 1 37 17·6 23·7 301 299 311

All lenses 10 28·9 þ 11·3 18·0 þ 13·4 18·5 þ 8·7 311 þ 8 303 þ 7 308 þ 6

Evaporation ¼ £ 1027 g cm22 sec21, Osmolarity ¼ milliosmoles/millilter. DW: daily wear contacts, RGP: rigid gas permeable contacts.

W. Mathers / Experimental Eye Research 78 (2004) 389–394 393

Brubaker, R.F., Maurice, D., McLaren, J.W., 1990. Fluorometry of the

anterior segment. In: Masters, B.R., (Ed.), Noninvasive Diagnostic

Techniques in Ophthalmology, Springer, New York, pp. 248–280.

Caffery, B.E., Richter, D., Simpson, T., Fonn, D., Doughty, M., Gordon, K.,

1998. CANDEES. The Canadian Dry Eye Epidemiology Study. Adv.

Exp. Med. Biol. 438, 805–806.

Cammenga, H.K., Koenemann, D., 1987. Continuous recording of the

evaporation rate of water through monolayers. Thin Solid Films 159,

53–61.

Cedarstaff, T.H., Tomlinson, A., 1983. A comparative study of tear

evaporation rates and water content of soft contact lenses. Am.

J. Optometry Physiol. Optics 60, 167–174.

Craig, J.P., Tomlinson, A., 1997. Importance of the lipid layer in human

tear film stability and evaporation. Optometry Vision Sci. 74, 8–13.

Craig, J.P., Singh, I., Tomlinson, A., Morgan, P.B., Efron, N., 2000. The

role of tear physiology in ocular surface temperature. Eye 14 Pt 4,

635–641.

Gilbard, J.P., 1996. Dry eye: pharmacological approaches, effects, and

progress. CLAO J. 22, 141–145.

Gilbert, T.E., Tator, K., 1971. Rate of evaporation of liquids into air. J. Paint

Technol. 43, 93–97.

Goto, E., Endo, K., Suzuki, A., Fujikura, Y., Matsumoto, Y., Tsubota, K.,

2003. Tear evaporation dynamics in normal subjects and subjects with

obstructive meibomian gland dysfunction. Invest. Ophthalmol. Visual

Sci. 44, 533–539.

Hamano, H., 1981. The change of precorneal tear film by the application of

contact lenses (Japanese). Contact Intraocluar Lens Med. J. 7, 205–209.

Hamano, H., Hori, M., Kawabe, H., Mitsunaga, S., Ohnishi, Y., Koma, I.,

1980. Modification of the superficial layer of the tear film by the

secretion of the meibomian glands. Folia Ophthalmol. Japonica 31,

353–360.

Hart, D.E., Simko, M., Harris, E., 1994. How to produce moisture chamber

eyeglasses for the dry eye patient. J. Am. Optometric Assoc. 65,

517–522.

Hickman, K.C.D., Torpey, W.A., 1954. Evaporation of resting water.

Engng Des Process Dev. 46, 1446–1450.

Hisatake, K., Tanaka, S., Aizawa, Y., 1993. Evaporation rate of water in a

vessel. J. Appl. Physiol. 11, 7395–7401.

Iwata, S., Lemp, M., Holly, F.J., Dohlman, C.H., 1969. Evaporation rate of

water from the procorneal tear film and cornea in the rabbit. Invest.

Ophthalmol. 8, 613–619.

Jordan, A.J.L. B, 1980. Basic tear flow: does it exist? Ophthalmology 87,

920–930.

Kaplon, J., Kawala, Z., Skoczlas, A., 1986. Evaopration rate of a liquid

from the surface of a rotating disc in high vacuum. Chem. Engng Sci.

41, 519–522.

Korb, D.R., Greiner, J.V., Glonek, T., 2001. The effects of Anionic and

Zwitterionic phospholipids on the tear film lipid layer. Invest.

Ophthalmol. Vision Sci.—Abstr. 42, S35.

LaMer, V.K., Barnes, G.T., 1959. The effects of spreading technique an

purity sample on the evaporation resistance of monolayers. Proc. Natl

Acad. Sci. US Am. 45, 1274–1280.

Mathers, W.D., 1993. Ocular evaporation in meibomian gland dysfunction

and dry eye. Ophthalmology 100, 347–351.

Mathers, W.D., Daley, T.E., 1996. Tear flow and evaporation in patients

with and without dry eye. Ophthalmology 103, 664–669.

Mathers, W.D., Lane, J.A., 1998. Meibomian gland lipid, evaporation,

and tear film stability. In: Sullivan, D.A, (Ed.), Lacrimal Gland, Tear

Film, and Dry Eye Syndromes, vol. 2. Plenum, New York, pp.

349–360.

Mathers, W.D., Binarao, G., Petroll, M., 1993. Ocular water evaporation

and the dry eye. A new measuring device. Cornea 12, 335–340.

Mathers, W.D., Lane, J.A., Sutphin, J.E., Zimmerman, M.B., 1996. Model

for ocular tear film function. Cornea 15, 110–119.

Mathers, W., Dolney, A.M., Kraemer, D., 2002. The effect of hormone

replacement therapy on the symptoms and physiologic parameters of

dry eye. In: Sullivan, D.A., (Ed.), Lacrimal Gland, Tear Film, and Dry

Eye Syndromes, vol. 3. Plenum, New York, pp. 1017–1022.

Maurice, D., 1995. The effect of the low blink rate in rabbits on topical drug

penetration. J. Ocular Pharmacol. Ther. 11, 297–304.

McCarty, C.A., Bansal, A.K., Livingston, P.M., Stanislavsky, Y.L., Taylor,

H.R., 1998. The epidemiology of dry eye in melbourne, australia.

Ophthalmology 105, 1114–1119.

McCulley, J.P., Shine, W.E., 2000. Changing concepts in the diagnosis and

management of blepharitis. Cornea 19, 650–658.

McMonnies, C.W., Ho, A., 1987. Responses to a dry eye questionnaire

from a normal population. J. Am. Optometric Assoc. 58, 588–591.

Mishima, S., Maurice, D.M., 1961. The oily layer of the tear film and

evaporation from the corneal surface. Exp. Cell Res. 1, 39–45.

Mishima, S., Gasset, A., Klyce, S.D. Jr., Baum, J.L., 1966. Determination

of tear volume and tear flow. Invest. Ophthalmol. 5, 264–276.

Rolando, M., Refojo, M.F., 1983. Tear evaporimeter for measuring water

evaporation rate from the tear film under controlled conditions in

humans. Exp. Eye Res. 36, 25–33.

Rolando, M., Refojo, M.F., Kenyon, K.R., 1983. Increased tear evaporation

in eyes with keratoconjunctivitis sicca. Arch. Ophthalmol. 101,

557–558.

Rosano, H.L., LaMer, V.K., 1956. The rate of evaporation of water through

monlayers of esters, acids and alcohols. J. Phys. Chem. 60, 348–353.

Schaumberg, Sullivan, D.A., Dana, M.R., 2000. Hormone replacement

therapy (HRT) and the prevelence of dry eye symptoms. Invest.

Ophthalmol. Visual Sci. 41, S740–S740.

Schein, O.D., Munoz, B., Tielsch, J.M., Bandeen-Roche, K., West, S.,

1997. Prevalence of dry eye among the elderly. Am. J. Ophthalmol.

124, 723–728.

Shimazaki, J., Sakata, M., Tsubota, K., 1995. Ocular surface changes and

discomfort in patients with meibomian gland dysfunction. Arch.

Ophthalmol. 113, 1266–1270.

Tiffany, J.M., 1985. The role of meibomian secretion in the tears. Trans.

Ophthalmol. Soc. UK 104, 396–401.

Toda, I., Shinozaki, N., Tsubota, K., 1996. Hydroxypropyl methylcellulose

for the treatment of severe dry eye associated with Sjogren’s syndrome.

Cornea 15, 120–128.

Tomlinson, A., Trees, G.R., 1991. Effect of preservatives with artificial tear

solutions on tear film evaporation. Ophthal. Physiol. Optics 11, 48–52.

Tomlinson, A., Trees, G.R., Occhipinti, J.R., 1991. Tear production and

evaporation in the normal eye. Ophthal. Physiol. Optics 11, 44–47.

Tsubota, K., Yamada, M., 1992. Tear evaporation from the ocular surface.

Invest. Ophthalmol. Visual Sci. 33, 2942–2950.

Tsubota, K., Monden, Y., Yagi, Y., Goto, E., Shimmura, S., 1999. New

treatment of dry eye: the effect of calcium ointment through eyelid skin

delivery. Br. J. Ophthalmol. 83, 767–770.

Yamada, M., Tsubota, K., 1990. Measurement of tear evaporation from

ocular surface. Nippon Ganka Gakkai Zasshi—Acta Societatis

Ophthalmologicae Japonicae 94, 1061–1070.

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