Elsevier

Survey of Ophthalmology

Volume 52, Issue 4, July–August 2007, Pages 369-374
Survey of Ophthalmology

Major Review
The Correlation Between the Tear Film Lipid Layer and Dry Eye Disease

https://doi.org/10.1016/j.survophthal.2007.04.009Get rights and content

Abstract

Dry eye, also known as keratoconjunctivitis sicca, can be due either to insufficient tear production or excessive tear evaporation, both resulting in tear hyperosmolarity that leads to symptoms of discomfort and ocular damage. Additionally, the severity of dry eye symptoms appears to be correlated to lipid layer thickness. It is now generally recognized that increased evaporation due to a compromised lipid layer is one of the most common etiologies for hyperosmolarity of the tear film. Thus, therapies targeted at replenishing or stabilizing the lipid layer are key to the treatment of dry eye, either as monotherapy or in conjunction with therapies designed to enhance aqueous production.

Introduction

Dry eye, also known as keratoconjunctivitis sicca (KCS), can be due either to insufficient tear production or excessive tear evaporation, both resulting in tear hyperosmolarity that leads to symptoms of discomfort and ocular damage.9, 10 Hyperosmolarity has been shown to provide a proinflammatory stress to the ocular surface.17 Dry eye is a widespread but underdiagnosed disease affecting between 40 million and 60 million Americans (Lemp MA, Foulks GN, Devgan U, et al: The therapeutic role of lipids: managing ocular surface disease. Refract Eyecare Ophthamol 9[Suppl]:3–15, 2005). For both aqueous tear deficient (ATD) and evaporative dry eye (EDE), hyperosmolarity is a precipitating event leading to the pathological changes associated with dry eye: for ATD, the tear flow rate at which critical osmolarity occurs will depend on evaporation rate, and for EDE, the rate of evaporation that results in critical osmolarity will depend on the tear flow rate.1 Evaporation rate is influenced by six factors, including ambient conditions, hormonal regulation, blink rate, area of palpebral aperture, tear film compartments, and tear film lipid layer. Evaporative dry eye is caused by poor lid-globe congruity, increased ocular exposure, reduced blink rate, unfavorable environmental conditions, and, most frequently, meibomian gland dysfunction.1

The tear film is a complex, dynamic structure of lipids, proteins, and mucins riding on the hydrophobic surface of the epithelium. The largest component of the tear film, almost 90%, is the aqueous product of the lacrimal glands, the output of which is usually referred to as the tear production.19 The outermost layer of the tear film, the tear film lipid layer (TFLL), is a combination of polar and nonpolar lipids that are the secretion of the meibomian glands, which are tubulo-acinar, holocrine glands that discharge their entire contents in the process of secretion.1, 2 Embedded in the tarsal plates, there are approximately 30–40 of these glands in the upper lid and 20–30 in the lower lid.2, 24 Each meibomian gland consists of a main duct surrounded by grapelike acinar clusters. These ducts open onto the lid margin skin just anterior to the mucocutaneous junction. Through these orifices meibum is steadily delivered into the marginal reservoirs and then spread over the pre-ocular tear film in the up-phase of each blink.5, 24 It has been estimated that in a normal adult male there are about 300 μg of meibomian lipid in the marginal reservoir and 9 μg of lipid in the pre-ocular film.2 The low melting point of the lipids (19–32°C) facilitates delivery to the tear film by allowing the secretion to remain fluid given the temperature of the surrounding tissue (37°C).32 The secretion of the meibomian glands is approximately 77% wax and sterol esters, 8% phospholipids, and 9% di- and triglycerides and hydrocarbons, but variations in this distribution account for the variability in melting point.20

Section snippets

Importance of the Lipid Layer in Tear Film Function

Functions of the lipid layer include providing a smooth optical surface for the cornea, enhancing the stability of the tear film, enhancing the spreading of the tear film, preventing spillover of tears from the lid margin, preventing contamination of the tear film by sebum, and sealing the apposed lid margins during sleep. The chief function of the lipid layer, however, is to retard water evaporation from the surface of the open eye.8 Studies suggest that normally, much of the tear film lipid

Abnormalities of the Lipid Layer and Tear Film Function

The most common cause of increased evaporation from the eye is meibomian gland disease, which leads to a reduced delivery of oil to the lid margin and to the tear film.1, 7, 8 Reduced delivery can, on rare occasions, be the consequence of congenital deficiencies, such as meibomian gland aplasia or dysplasia, or distichiasis, in which the meibomian glands are replaced by an extra row of lashes. More common, however, is the occurrence of meibomian gland dysfunction (MGD), which may be defined as

Therapy of Lipid Layer Abnormalities

It has been demonstrated that treatment of MGD through manual expression of the meibomian glands does increase the tear film lipid layer thickness and tear film stability.3, 15 The Craig study measured the non-invasive break-up time (NIBUT) and the tear thinning time (TTT) of normal eyes after manual expression of meibomian lipid and found that both the NIBUT and TTT was significantly higher in the treated eyes in comparison to the untreated eyes. This study showed that increasing the thickness

Summary

Overall, decades of research has shown a strong correlation between dry eye symptoms and the state of the tear film lipid layer, as well as a clear connection between the status of the lipid layer and the osmolarity of the tear film. Treatment of the meibomian glands with mechanical and medicinal measures has proven effective in increasing the thickness and stability of the TFLL, and more recent work with supplementation of the tear film lipids has also shown effectiveness in stabilizing the

Method of Literature Search

Literature selection for this review was based on a Medline database search using the terms meibomian gland dysfunction, tear film, lipid layer thickness, dry eye disease, and evaporative dry eye from the period 1966 to the present. Pertinent articles from the English-language journals only were selected. The articles referenced were primarily from 1991 to 2006 and relevant references contained within those articles were gathered.

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      The steady flow of warm exhaled air adversely affects the tear film homeostasis by causing increased tear evaporation. The outermost lipid layer plays a significant role in maintaining tear film stability and preventing its evaporation, and is directly affected by exhaled air.17,18 A key finding in the current study was an increase in tear film LLT after taping the upper mask edge, with a corresponding increase in TBUT.

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    The author reported no proprietary or commercial interest in any product mentioned or concept discussed in this article. The author acknowledges the assistance of Judith Burdan, PhD, in preparing this manuscript. The author is a paid consultant to Alimera Sciences, Inc, the manufacturer of Restoryl. Alimera Sciences paid for the reprints available for this review.

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