by Noelle La Croix, DVM, Dip. ACVO
Keratoconjunctivitis Sicca – Part 1: Structure of the Tear Film
The precorneal tear film
The precorneal tear film is essential for the health and function of the ocular surface. As the first refractive surface of the eye, the tear film’s health is also necessary for visual clarity. It consists of four complex layers of tissue secretions and epithelia. The innermost layer is a glycocalyx extending outward form corneal and conjunctival epithelia. This is covered by a layer of mucus, a third aqueous layer, and finally an outer layer of lipids (Figure 1). The layering is not fixed and distinctive, but rather blends into a flowing liquid that coats the corneal surface.
Keratoconjunctivitis sicca (KCS or dry eye syndrome) is classically described as a deficiency in the aqueous layer of the tear film. However, KCS can be thought of as a syndrome comprising a number of abnormalities of the tear film and/or ocular surface. There are both extrinsic and intrinsic etiologies of KCS including diseases of the eyelids, meibomian glands, ocular surface, and neural network. Keratoconjunctivitis sicca is commonly associated with pain, decreased visual acuity, corneal vascularization, corneal pigmentation, corneal and eyelid infection, corneal rupture, and/or ocular necrosis. The diagnosis of KCS begins with a systemic evaluation of each component of the tear film. Appropriate treatments are then applied to re-establish the functionality of, or to replace, any unhealthy elements that are discovered.
The glycocalyx and mucous layer
The innermost layer of the tear film consists mainly of carbohydrates extending from corneal and conjunctival epithelia. Mucin proteins secreted by corneal and conjunctival squamous cells are also found within this glycocalyx. The mucins form a lubricating gel that moves the tear film relative to ocular movements and during blinking. In addition, mucins hydrate the corneal surface and act as a barrier to invading pathogens.
Some mucins of the glycocalyx remain membrane-bound but extend into an outer mucous layer. Gel-forming mucins (secreted by goblet cells interposed between stratified conjunctival squamous cells) are the other major component of this mucous layer. Goblet cell mucin production and secretion is regulated by both parasympathetic and sympathetic stimulation, and by the level of water secreted by neighboring conjunctival cells. The proliferation of these goblet cells is regulated by numerous growth factors.
The aqueous layer and neuronal control
The third layer of the tear film is formed by aqueous secretions of the nictitans and lacrimal glands. A negligible amount of this aqueous layer is also secreted by conjunctival and corneal squamous epithelia. Both afferent and efferent trigeminal nerves regulate lacrimation (tear production). The afferent trigeminal nerves ultimately conduct sensory stimuli from the cornea, adnexa, nictitans glands, and lacrimal glands to the brain. Efferent trigeminal nerves then respond by stimulating the lacrimal and nictitans glands. Stimulation of the cornea and/or adnexa typically increases lacrimation and is known as ‘reflexive lacrimation.’ Burning and other painful sensations in the eye typically cause reflexive lacrimation (e.g., crying in response to propanethiol S-oxide gas released by onion slicing). This response probably evolved to flush irritants from the ocular surface.
Tear production can also be stimulated in the absence of noxious stimuli. Basal levels of lacrimation result from continuous stimulation of corneal nerve endings. For example, the decreases in corneal nerve sensitivity of diabetics can result in their subsequent reductions in lacrimation. Corneal nerves also release tropic substances that promote the integrity and overall health of the cornea. These substances are particularly important in the resolution of corneal wounds. Therefore, sensory damage of corneal nerves may promote corneal ulceration in addition to KCS.
Efferent trigeminal nerves distribute autonomic nerve fibers to both the lacrimal and nictitans glands. Parasympathetic (and possibly sympathetic) nerves modulate lacrimation. Preganglionic parasympathetic neurons originate from parasympathetic nuclei of facial nerves (the rostral salivary nuclei). Efferent neurons of the rostral salivary nuclei are found within the rostral portion of the medulla oblongata, and their fibers exit the brain through the facial canals. Preganglionic parasympathetic nerves split at the geniculate ganglion of the facial nerves within the dorsal aspect of the petrous temporal bones. These nerves (which together form the major petrosal nerves) pass through the petrous temporal bones and are associated with the eustachian tubes. The nerves then join with the deep petrosal nerves forming the nerves of the pterygoid canal. The parasympathetic aspect of these nerves then synapse with the pterygopalatine ganglia located upon the pterygoideus medial muscles within the floor of each orbit. Postganglionic parasympathetic neurons follow the zygomatic nerves (the first branch of the maxillary division of the trigeminal nerves) and synapse with the acinar of the lacrimal glands.
The lipid layer
The lipid layer is secreted by the meibomian glands lining the upper and lower eyelid margins. These glands secrete a mixture of proteins and lipids (meibum) forming a liquid at physiologic temperatures. Minute amounts of meibum are secreted during blinking and form a lipid reservoir in the inferior portion of the tear film. The eyelids spread lipids throughout the tear film during upward blinking. Downward blinking returns lipids to the inferior reservoir. Meibum forms a hydrophobic that prevents tear outflow onto the eyelids, and prevents eyelid sebum from entering the tear film. This hydrophobic layer also prevents evaporation of the tear film, and smoothes eyelid movement over the cornea and conjunctiva. The nerves that stimulate meibum secretion by the meibomian glands are not known.
Eyelids and the coordination of tear secretion
Blinking of the eyelids helps maintain a healthy precorneal tear film. Each blink initiates a cycle of secretion, dispersal, evaporation, and drainage of the tear film. Paralysis or delayed blinking can therefore result in KCS or reflexive tearing. However, canine facial nerve paralysis is not always associated with KCS. In these cases, the third eyelid may absorb the function of the eyelids in preserving the tear film.
An appropriate level of tear secretion results from a coordinated process. Aqueous and mucus secretions are regulated by neuronal reflexes. Conjunctival and corneal nerves are initially activated by sensory stimuli. The stimulated nerves affect efferent parasympathetic and sympathetic nerves that regulate secretions of the lacrimal glands (aqueous) and goblet cells (mucus). Blinking spreads a thin layer of lipids (secreted by the meibomian glands) over the tear film surface. The rate of lacrimation normally balances the rates of tear evaporation and nasolacrimal drainage. The rate of nasolacrimal drainage can be affected by corneal stimuli. Corneal stimulation can restrict or dilate the blood supply of the cavernous sinus of the tear drainage ducts. Vasodilation or vasoconstriction will then increase or decrease the nasolacrimal ducts’ lumenal dimensions, and therefore affect tear drainage rates. The tear film’s evaporative rate will vary with its exposure time between blinks, air temperature, humidity, and air speed.
My next article will explore treatment option for KCS. If you have further questions regarding the components of the tear film please feel free to consult a veterinary ophthalmologist.
Noelle La Croix, DVM, Dip. ACVO
Veterinary Medical Center of Long Island
75 Sunrise Highway
West Islip, New York 11795
(631) 587-0800; fax (631) 587-2006
Figure 1: The precorneal tear film consists of four complex layers of tissue secretions and epithelia.