Elsevier

The Ocular Surface

Volume 16, Issue 1, January 2018, Pages 4-30
The Ocular Surface

Review
Mechanisms, imaging and structure of tear film breakup

https://doi.org/10.1016/j.jtos.2017.09.007Get rights and content

Abstract

Tear film breakup (BU) is an important aspect of dry eye disease, as a cause of ocular aberrations, irritation and ocular surface inflammation and disorder. Additionally, measurement of breakup time (BUT) is a common clinical test for dry eye. The current definition of BUT is subjective; here, a more objective concept of “touchdown” – the moment when the lipid layer touches down on the corneal surface - is proposed as an aid to understanding processes in early and late stages of BU development. Models of BU have generally been based on the assumption that a single mechanism is involved. In this review, it is emphasized that BU does not have a single explanation but it is the end result of multiple processes. A three-way classification of BU is proposed – “immediate,” “lid-associated,” and “evaporative.” Five different types of imaging systems are described, which have been used to help elucidate the processes involved in BU and BUT; a new method, “high resolution chromaticity images,” is presented. Three directions of tear flow - evaporation, osmotic flow out of the ocular surface, and “tangential flow” along the ocular surface - determine tear film thinning between blinks, leading to BU. Ten factors involved in BU and BUT, both before and after touchdown, are discussed. Future directions of research on BU are proposed.

Section snippets

Aims and scope

Breakup (BU) is an important but poorly understood aspect of the tear film and dry eye disorders. The aim of this review is to describe the wide range of imaging methods for studying tear BU and to propose mechanisms and structure for BU that incorporate current understanding of the fluid dynamics involved. Much of the information presented in this review is based on the authors' experience and thus is descriptive rather than quantitative.

The following areas are covered in this review. First,

Definition of breakup

According to the 2007 Dry Eye Workshop [1], “the tear film breakup time is defined as the interval between the last complete blink and the first appearance of a dry spot or disruption in the tear film.” The “first appearance of a dry spot” may relate to the appearance of a dark area in FBUT, whereas the “disruption of the tear film” may correspond to distortions of the tear surface seen in NIBUT. Lemp and Hamill [18] added that, from trial to trial, the BU position should be randomly located,

Breakup time is an important clinical test of tear film function

Together with the Schirmer test, staining tests, and history, FBUT is one of the preferred diagnostic tests for dry eye used by eye care practitioners [67]; since that report, osmolarity testing has become another common test [68]. Abelson et al. [69] found a normal mean FBUT of 7.1 s, which was reduced to 2.2 s in dry eye; they recommended a cutoff for dry eye diagnosis of ≤5 s, while previous studies proposed a cut off of 10 s [70], [71]. It may be noted that a larger cutoff value increases

Surface physical chemistry models

An early model and much referenced paper by Holly [13] was based on ideas from surface physical chemistry; the model involved diffusion of lipids through the aqueous layer, causing the mucus layer to become hydrophobic and thus generating BU. A critical review of this and other models based largely on physical chemistry of the mucus layer and corneal surface has been published by Peng et al. [55] A limitation of such models has sometimes been imperfect in vivo experimental evidence; for

Classification of breakup

BU is a complicated and still poorly understood process, so a complete classification of BU is probably not possible at present. In the classification proposed here, we have tried to distinguish three types of BU, which depend mainly on different mechanisms and can be differentiated from each other quite readily.

BU has sometimes been classified by shape of the BU area. Bitton and Lovasik [107] described three distinct patterns – “dots” with a circular shape, “streaks” having a linear shape, and

Images of breakup obtained by different methods

In this review, the importance of different imaging methods for studying mechanisms of BU is emphasized. Five different types of methodology for imaging the tear film are illustrated in Fig. 6 and will be reviewed in this section. Note that both the tear and corneal surfaces are rough, so both can contribute to spatial variations in tear film thickness. This may be expressed by the equationh(x,y,t) = a(x,y,t)-c(x,y,t)where h is tear film thickness, x and y give position on the tear surface, t

Three directions of tear flow determine tear thinning and breakup

Tear film thickness changes within a small area of tear film are determined by three directions of tear flow [34]. First, water may flow outwards into the air by evaporation causing tear thinning. Second, water may flow across the corneal surface, typically by osmosis [142]; in the interblink interval, evaporation causes increased tear osmolarity and hence osmotic flow into the tear film, tending to oppose tear film thinning. Third, there may be “tangential flow” (flow along the corneal

Ten factors in tear film breakup and breakup time

Section 7 listed three directions of tear flow, which determine the thinning of the tear film, leading to BU. This section elaborates a number of factors that affect these three directions of flow. In addition, the initial thickness of the tear film deposited by a blink [111] is discussed because it is an important factor in BUT. Finally, factors involved in causing touchdown and after touchdown will also be considered.

Future directions

There is an important need for a more quantitative understanding of the processes involved in BU and BUT. This applies to the thinning of the tear film before touchdown (Fig. 1, Fig. 17), as well as the processes after touchdown. In Section 7, three directions of tear flow contributing to, or countering, tear film thinning were discussed, namely evaporation, flow across the corneal surface (osmotic flow), and tangential flow along the corneal surface. The relations between these three

Conclusions

Tear film BU is an essential characteristic of dry eye. BUT is reduced in dry eye, so it is an important clinical test. BU often causes high PCTF osmolarity and may sometimes cause mechanical shear of the cornea; hence, BU stresses the corneal surface causing irritation and inflammation.

The definition of BU suffers from uncertainty (does the tear film form a dry spot?) and lack of objectivity (e.g., how dim should fluorescence be at BU?). It is proposed that a more objective definition would be

Acknowledgement

The authors have no commercial or proprietary interest in any product or concept described in this article.

Financial support: RO1 EY017951 (King-Smith), RO1 EY021794 (Begley), NSF 1412085 (Braun).

References (178)

  • P.E. King-Smith et al.

    High resolution microscopy of the lipid layer of the tear film

    Ocul Surf

    (2011)
  • R.J. Braun et al.

    Dynamics and function of the tear film in relation to the blink cycle

    Prog Retin Eye Res

    (2015)
  • C.C. Peng et al.

    Evaporation-driven instability of the precorneal tear film

    Adv Colloid Interface Sci

    (2014)
  • R.A. Cone

    Barrier properties of mucus

    Adv Drug Deliv Rev

    (2009)
  • C. Belmonte et al.

    Neural basis of sensation in intact and injured corneas

    Exp Eye Res

    (2004)
  • M. Al-Abdulmunem

    Relation between tear breakup time and spontaneous blink rate

    Int Contact Lens Clin

    (1999)
  • K. Nakamori et al.

    Blinking is controlled primarily by ocular surface conditions

    Am J Ophthalmol

    (1997)
  • E. Goto et al.

    Impaired functional visual acuity of dry eye patients

    Am J Ophthalmol

    (2002)
  • T.J. Millar et al.

    The real reason for having a meibomian lipid layer covering the outer surface of the tear film - a review

    Exp Eye Res

    (2015)
  • The definition and classification of dry eye disease: report of the definition and classification subcommittee of the international dry eye WorkShop

    Ocul Surf

    (2007)
  • M.S. Norn

    Desiccation of the precorneal film. I. Corneal wetting-time

    Acta Ophthalmol (Copenh)

    (1969)
  • P.E. King-Smith et al.

    Contributions of evaporation and other mechanisms to tear film thinning and breakup: a review

    Optom Vis Sci

    (2008)
  • M.S. Norn

    Desiccation of the precorneal film. II. Permanent discontinuity and dellen

    Acta Ophthalmol (Copenh)

    (1969)
  • N. Yokoi et al.

    Tear film oriented diagnosis and therapy for dry eye

  • H. Liu et al.

    Temporal progression and spatial repeatability of tear breakup

    Optom Vis Sci

    (2006)
  • R.H. Rengstorff

    The precorneal tear film: breakup time and location in normal subjects

    Am J Optom Physiol Opt

    (1974)
  • D.Q. Li et al.

    Stimulation of matrix metalloproteinases by hyperosmolarity via a JNK pathway in human corneal epithelial cells

    Invest Ophthalmol Vis Sci

    (2004)
  • H. Liu et al.

    A link between tear instability and hyperosmolarity in dry eye

    Invest Ophthalmol Vis Sci

    (2009)
  • S.C. Pflugfelder

    Tear dysfunction and the cornea: LXVIII edward jackson memorial lecture

    Am J Ophthalmol

    (2011)
  • Z. Liu et al.

    Corneal thickness is reduced in dry eye

    Cornea

    (1999)
  • R. Pfister et al.

    The histopathology of experimental dry spots and dellen in the rabbit cornea: a light microscopy and scanning and transmission electron microscopy study

    Invest Ophthalmol Vis Sci

    (1977)
  • I. Fatt

    Observations of tear film break up on model eyes

    CLAO J

    (1991)
  • F.J. Holly

    Tear film formation and rupture: an update

  • D.R. Korb et al.

    Corneal staining subsequent to sequential fluorescein instillations

    J Am Optom Assoc

    (1979)
  • M.A. Lemp et al.

    Factors affecting tear film breakup in normal eyes

    Arch Ophthalmol

    (1973)
  • L.S. Mengher et al.

    A non-invasive instrument for clinical assessment of the pre-corneal tear film stability

    Curr Eye Res

    (1985)
  • S. Patel et al.

    Effects of fluorescein on tear breakup time and on tear thinning time

    Am J Optom Physiol Opt

    (1985)
  • R.K. Madden et al.

    Comparative study of two non-invasive stability techniques

    Curr Eye Res

    (1994)
  • K. Gumus et al.

    Noninvasive assessment of tear stability with the tear stability analysis system in tear dysfunction patients

    Invest Ophthalmol Vis Sci

    (2011)
  • L.E. Downie

    Automated tear film surface quality breakup time as a novel clinical marker for tear hyperosmolarity in dry eye disease

    Invest Ophthalmol Vis Sci

    (2015)
  • J. Nemeth et al.

    High-speed videotopographic measurement of tear film build-up time

    Invest Ophthalmol Vis Sci

    (2002)
  • D.H. Szczesna et al.

    Lateral shearing interferometry, dynamic wavefront sensing, and high-speed videokeratoscopy for noninvasive assessment of tear film surface characteristics: a comparative study

    J Biomed Opt

    (2010)
  • T. Kamao et al.

    Screening for dry eye with newly developed ocular surface thermographer

    Am J Ophthalmol

    (2011)
  • T.J. Licznerski et al.

    Application of Twyman-Green interferometer for evaluation of in-vivo breakup characteristic of the human tear film

    J Biomed Opt

    (1999)
  • J.D. Micali et al.

    Dynamic measurement of the corneal tear film with a Twyman-Green interferometer

    J Biomed Opt

    (2015)
  • A. Dubra et al.

    Double lateral shearing interferometer for the quantitative measurement of tear film topography

    Appl Opt

    (2005)
  • H. Hamano et al.

    The physiology of the cornea and contact lens applications

    (1987)
  • P.E. King-Smith et al.

    Application of a novel interferometric method to investigate the relation between lipid layer thickness and tear film thinning

    Invest Ophthalmol Vis Sci

    (2010)
  • J.J. Nichols et al.

    Thinning rate of the precorneal and prelens tear films

    Invest Ophthalmol Vis Sci

    (2005)
  • A. Sharma

    Energetics of corneal epithelial cell-ocular mucus-tear film interactions: some surface-chemical pathways for corneal defense

    Biophys Chem

    (1993)
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