Bringing Tears to Your Eyes
Knowledge of the physiology of the tear film enables you to better isolate, identify and classify in vivo ocular surface problems.
SCOT MORRIS, O.D. F.A.A.O., Conifer, Colo. and
TRISHA C. ROGERS, O.D., Conifer, Colo.
The tear film has three separate currents of fluid, or layers, each of a different viscosity and each moving in a different direction. What’s more: The direction of each current changes with every blink, and the surrounding environment continually affects this intricate balance.
While all this goes on, each layer must maintain a significant enough tear volume to provide its necessary function. In other words, the rate of production of each layer changes throughout the day, with age, medication use and hormone alterations, among other factors. In fact, the rate of evaporation of each layer varies depending on environmental conditions, blink rate and overlying lipid characteristics.
Further, the rate of clearance (or drainage) of the viscosity of the tear medium as a whole also fluctuates with rates of tear production, evaporation, canalicular lumen size, force and blink speed.
|
This image provides a magnified view of the normal tear film and all its components. |
With all these activities taking place, it’s no wonder we, as eyecare practitioners and scien-tists, have difficulty isolating, identifying and classifying ocular surface problems in vivo. (See “Understanding Tear Film Function,” page 50.)
By reviewing the normal physiology of the tear film, however, you have a better chance of isolating, identifying and classifying ocular surface problems in your patients. This is because as with any physiological problem, you must first know how the environment should perform in normal conditions to determine what’s not functioning correctly when it’s in a diseased state.
Here, we will review the following tear-film subgroups: the lipid layer, mucin-aqueous complex, ocular surface and the palpebral conjunctival surface and the eyelids. Please remember, however, that each group directly and indirectly affects the overall intricate balance of the tear film as a whole.
The lipid layer
The lipid layer contains mei-bum, a mixture of waxy esters, sterols, cholesterol, polar lipids and free fatty acids that are liquid at room temperature.1,2,3,4,5 Mei-bum is produced by 30 to 40 meibomian glands in the superior lid and 20 to 30 in the lower lid.
These holocrine glands are tubuloacinar, yellow, grape-like clusters with central secretory ducts that deliver secretion to the lid surface. The lipid is then deposited on to the anterior aspect of the tears through orifices flush with the lid surface.1,2,4
The lipid layer is on average only 68nm thick.1 Though a basal secretion rate may be present, the majority of meibum is excreted by pressure induced from contraction of the orbicularis oculi with each blink.1,6 After each blink, surface tension pulls the lipid upward. The mei-bum lubricates the lid surface, reduces evaporation, provides a barrier to the polar cutaneous sebum, forms a hydrophobic seal between the lids during sleep and stabilizes the tear film by increasing surface tension.7 Researchers have theorized that the sex hormone androgen, in part, controls meibum production.8 Increased androgen levels and a cholinergic agonist response may increase meibum production while anti-androgens and estrogen may act to suppress production.1,2
The mucin-aqueous complex
The mucin layer and aqueous layer are a continuance of each other. Mucins are actually hydrated glycoproteins produced by the bulbar and fornical conjunctiva goblet cells. Adsorbed or transmembrane mu-cins (MUCIN 1 and 4) are tightly bound to the ocular surface. These mucins create a hydro-philic substrate that provides a transition between the hydro-phobic cell surface and the hydrophilic outer layers of the tear film. Free-floating mucins (MUCIN 5AC) are mixed homo-genously with the aqueous secretions to create the aqueous mucin gel. Mucin allows for a thinner tear film, stabilizes the tear film against the shear forces of the blink and serves as a primary vehicle for removal of tear-film debris and contaminated lipids that “sink” into the mucin gel. Parasympathetic agonists, histamines, chemical irritants and prostaglandins can all stimulate mucin production. Researchers have observed that the goblet cell density is four times greater in the palpebral conjunctiva than in the interpalpebral bulbar conjunctiva. They have also noted that the mucin layer is thicker over the conjunctiva, especially nasally, and thinner over the corneal epithelial cells.9 The corneal mucin layer may range from 0.4µm to 1.0µm; whereas the conjunctival layer may be as thick as 7µm depending on its location.1,3,9,10 The fact that the mu-cin layer has varying thickness levels has been a fighting point among some tear manufacturers.
The aqueous is a hypotonic solution composed of antibacterial proteins (lysozyme and lac-toferrin), albumin, fibroblast growth factor, nerve growth factor, immunoglobulins and other proteins, as well as glucose, gly-cogen, oxygen, urea and other inorganic salts that provide nutrients to the avascular anterior cornea.11,12 (Remember: Salts can be organic — complex carbon-based salt molecules — or inorganic — common table salt. The body takes in, processes and excretes both types.) Researchers have found that the lacrimal gland secretes various cytokines, including epidermal growth factor (EGF) and transforming growth factor beta-1 (TGF-b1), into the aqueous. Researchers believe these components maintain homeostasis and promote a healthy ocular surface.13
The aqueous travels from the main lacrimal gland and accessory glands, through small lacri-mal ducts and is deposited onto the ocular surface at the superior lateral fornices. It’s then spread by surface tension and action of the lids across the ocular sur-face in an inferior nasal direction, though every blink cycle interrupts this flow pattern. Tear secretion is in part, if not wholly, reflex in origin. The lacrimal glands are under autonomic control via the trigeminal nerve and a neuronal feedback loop. The minimal secretion rate is unknown and likely depends upon many individual factors, such as hormone status and systemic medication use, among others. However, the approximate flow is 1.2µm/1min.
The ocular surface
The ocular surface, composed of both corneal and conjuncti-val epithelium, contains various subtypes of epithelial cells. Both the conjunctival and corneal epithelium are composed of stratified, non-keratinized epithelial cells. The corneal epithelium secretes a tightly bound glycoprotein on the surface known as the glycocalyx.14 This glycocalyx allows the mucin to maintain contact with the hydrophobic epithelium. Mucin-producing goblet cells are interspersed throughout the conjunctival epithelium with greater density in the nasal fornical and bulbar conjunctiva. Fine sensory nerve filaments innervate the ocular surface, penetrate Bowman’s layer and extend into the basal epithelial layers, as well as the conjunctiva. These sensory filaments are extensions of a greater network interlaced through the stromal lamellae and episclera that originate from the ophthalmic nerve. These sensory filaments make up part of the neurosensory feedback loop that drives reflex tear secretion.
Understanding Tear Film Function Undoubtedly, the tear film is a very complex kinetic medium. It’s dynamic in its composition, structure and function. The tear film also has multiple functions that are crucial to both health and vision. • The tear film provides a smooth optical surface and forms one of the most important refracting surfaces of the eye. In a diseased state, the quality of the tear prism degrades, and visual fluctuation is common. • A fine balance of mucin, aqueous and lipid constitutes the tear film and forms a protective barrier to bacteria, facial sebum, evaporation and desiccation. In diseased states, this balance is disrupted, and the ocular surface is no longer protected in the same manner, allowing various pathological changes to occur on the ocular and palpebral surface. • The tear film lubricates the bulbar-lid surfaces. If sufficient lubrication isn’t present, morphological changes to the surface epithelium may result, leading to an array of conditions, such as squamatization, increased surface shearing and potentially even keratinization. • The tear film provides the necessary nutrients and electrolyte balance to the ocular surface. In diseased states, this normal chemistry is altered, leading to cell apoptosis. • The tear film removes waste products from the ocular surface. Think of it as waste clean-up. As the tear film is altered, this clearance function changes, leading to a build-up of biochemical toxins and exogenous materials, such as allergens, dust and other solutes. In other words, what would happen if the garbage man forgot to pick-up the trash for a few months? Even subtle alterations in any of the tear film substrates or the ocular surface itself can change any of these functions. |
The palpebral conjunctival surface and the eyelids
Lid architecture and contact relationship with the ocular surface and, more specifically, the tear film, play a vital role in tear-flow dynamics. Think of your lid as a windshield wiper. As the lid comes down, it “spreads” or “wipes” the tear film across the ocular surface. If a windshield wiper has any points of non-contact with the windshield, you get a smear. In the eye, that may lead to tear-film stagnation or alterations in the normal tear-film balance.
Improper apposition can lead to drainage issues, as well as lipid deposition problems. These appositional issues, whether local or more geographic, can lead to tear-film “spread” issues.
Donald R. Korb, O.D., of Boston, has published some interesting work recently that shows a high correlation between dry-eye symptomatic patients and a condition called lid wiper epitheliopathy.15 In this condition, the small area of squamous epithelium found on the palpebral conjunctiva at the lid margin acts as a “windshield wiper” to the ocular surface. More interesting is that many times, clinical findings are absent with this disease, although the patients are symptomatic for dry eye. This was especially true in patients who had lipid-based issues. (See “Don’t Blink, and You’ll Miss it,” page 53.)
By familiarizing yourself with the normal physiology of the tear film, the way each tear-film sub-group is meant to function during blink and how each group directly and indirectly affects the overall intricate balance of the tear film as a whole, it will be easier for you to isolate, identify and classify ocular surface problems in your patients. This, in turn, will enable you to choose the appropriate treatment to al-leviate the various signs and symptoms of specific ocular surface problems in your patient population.
Don’t Blink And You’ll Miss It To understand the roles of the various segments of the tear film, you must comprehend what is truly happening before, during and after blink. So, let’s start from the split second after the lid closes during the blink sequence: As the upper lid margin comes in contact with the lower lid margin (and maybe as proposed by Dr. Korb), the lid wiper pulls the recently excreted lipid and the mucin-aqueous complex upward across the ocular surface. In the process, the lipid remains, in large part, superficial to the remaining layers of the tear film. The negative capillary action caused by the lid moving upward causes drainage of the tear lake in the medial canthus into the upper and lower punctum. The combination of the surface tension of the lipid layer and the hydrophobic transmembrane mucins allow the mucin-aqueous gel to remain relatively thin. While the eyelid is returning to its resting, open position, the lipid stabilizes on the ocular surface and begins to thicken inferiorly as the heavy polar lipids sink. As the lipid layer thins, the evaporation rate increases and, subsequently, the underlying aqueous starts to thin. As the tear film above the ocular and palpebral surfaces dissipates, the neural reflex loop is triggered. This starts the blink process, as well as the lacrimal secretion process. As the eyelid begins the next part of the blink sequence, the orbicularis oculi contracts, pulling the eyelids toward each other, thus spreading the newly secreted aqueous component across the ocular surface and down to the lower boundaries of the tear prism. Then, the process starts again. |
1. Driver PJ, Lemp MA. Meibomian gland dysfunction. Survey of Ophthalmology. 1996 March-April;40(5):343–367.
2. Bron AJ, Benjamin L, Snibson GR. Meibomian gland disease. Classification and grading of lid changes. Eye. 1991;5 (Pt4):395–411.
3. Holly FJ. Tear film physiology. Internatl Ophth Clinics. 1987 Spring 27(1):1–6.
4. Bron AJ, Mengher LS. Congenital deficiency of meibomian glands. Br J Ophthalmol. 1987 Apr;71(4):312–4.
5. Nichols KK, Ham BM, Nichols JJ, et al. Identification of fatty acids and fatty acid amides in human meibomian gland secretions. Invest Ophthalmol Vis Sci. 2007 Jan;48(1):34 –9.
6. Josephson JE. Appearance of the pre-ocular tear film lipid layer. Am J of Optom & Physio Optics. 1983 Nov.;60 (11):883–7.
7. Bowman RW, Dougherty JM, McCulley JP. Chronic blepharitis and dry eyes. International Ophthalmology Clinics. 1987 Spring;27(1):27–35.
8. Sullivan DA, Sullivan BD, Ullman MD, et al. Androgen influence on the meibomian gland. Invest Ophthalmol Vis Sci. 2000 Nov;41(12):3732–42.
9. Nichols BA, Chiappino ML, Dawson CR. Demonstration of the mucous layer of the tear film by electron micro-scopy. Invest Ophthalmol Vis Sci. 1985 Apr;26(4):464–73.
10. Lin SP, Brenner H. Tear film rupture. J Coll Interface Sci. 1982 89:226–231.
11. Van Haeringen NJ. Clinical biochemistry of tears. Surv Ophthalmol. 1981 Sept-Oct;26(2):84–96.
12. Nguyen DH, Beurman RW, Thompson HW, DiLoreto DA. Growth factor and neurotrophic factor mRNA in human lacrimal gland. Cornea. 1997 Mar;16(2):192–99.
13. Pflugfelder SC.Second International Conference on the Lacrimal Gland, Tear Film and Dry Eye Syndromes. November 16–19, 1996, South Hampton Parish, Bermuda.
14. Prydal JI, Artal P, Woon H, Campbell FW. Study of human pre-cor-neal tear film thickness and structure using laser interferometry. Invest. Ophthalmol Vis Sci. 1992 May;33(6): 2006–11.
15. Korb DR, Greiner JV, Herman JP, et al. Lid-wiper epitheliopathy and dry-eye symptoms in contact lens wearers. CLAO J. 2002 Oct;28(4):211–6.
|
|
![]({"src":"/media/xs2mkrsp/42007.jpg","focalPoint":null,"crops":[{"alias":"thumbnail","width":1110,"height":700,"coordinates":null}]})