Original article
The Pathology of Dry Eye

https://doi.org/10.1016/S0039-6257(00)00200-9Get rights and content

Abstract

Homeostasis of the tear film involves delicate hormonal and neuronal regulatory mechanisms. The eye appears to be a target organ for sex hormones, particularly the androgens, as they modulate the immune system and trophic functions of the lacrimal glands and the functioning of the meibomian glands. The cornea, lacrimal glands, mucous cells, and meibomian glands are all richly innervated, indicating the importance of nervous regulation in their function. Parasympathetic, sympathetic, and sensory innervation play complex stimulatory or inhibitory roles, and neuronal pathways interact via complex surface results cascades. Abnormalities at any point in these pathways can cause overall dysregulation of lacrimal function. Whatever the initial causes of dry eye, chronic dryness of the ocular surface results in inflammatory reactions and gradual destruction of the lacrimal glands and conjunctival epithelium. Once dry eye disease has developed, inflammation is the key mechanism of ocular surface injury, as both the cause and consequence of cell damage. In practice, dry eye can be associated with Sjögren's syndrome, allergies, infection, blepharitis, and preservative-containing eye drops.

Section snippets

Hormonal Regulation

Although the mechanisms of hormonal regulation of tear secretion remain poorly understood, the influence of sex hormones, and of androgens, in particular, appears to be of paramount importance. Androgens modulate the anatomy, physiology, and the immune system of the lacrimal gland in rats, rabbits, hamsters, and humans. Other hormones, such as luteinizing hormone, follicle stimulating hormone, prolactin, thyroid stimulating hormone, progesterone, and estrogens also appear to influence normal

Nervous Regulation

The cornea is very richly innervated, with 60 times more nerve endings than dental pulp, indicating the importance of nervous signals in the trophic regulation and protection of the cornea. The main and accessory lacrimal glands, mucous cells, and meibomian glands also have an abundant nerve supply. This comes mainly from the parasympathetic system (acetylcholine- and vasoactive intestinal peptide [VIP]–containing nerve terminals), but also from sympathetic nerves (neuropeptide Y and

Chronic Inflammation and Dry Eye Disease

Whatever the initial cause of dry eye disease, chronic dryness of the ocular surface results in excessive nervous stimulation aimed at triggering the mechanisms of regulation and repair. It has been hypothesized that these nervous stimuli lead to neurogenic inflammation, activation of T-cells, and the subsequent release of inflammatory cytokines into the lacrimal glands, tear film, and conjunctiva.51 Epithelial cells may independently produce interleukins 1α, 6, and 8, and tumor necrosis

Inflammation and Dry Eye in Practice

In clinical practice, dry eye disease can be assigned to two major classes: tear deficient dry eye and evaporative dry eye.13, 35 Tear deficient dry eye, the most common form, can be further classified into Sjögren's syndrome dry eye, an autoimmune disorder affecting the lacrimal and salivary glands, and non-Sjögren's syndrome dry eye, which encompasses the range of other causes of tear deficiency.

Acknowledgements

The author has no proprietary or commercial interest in any product or concept discussed in this article.

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