Chapter 4: Lids, Lacrimal Apparatus, & Tears
III. TEARS
Tears form a thin layer approximately 7-10 
m thick that covers the corneal and conjunctival epithelium. The functions of this ultrathin layer are (1) to make the cornea a smooth optical surface by abolishing minute surface epithelial irregularities; (2) to wet and protect the delicate surface of the corneal and conjunctival epithelium; (3) to inhibit the growth of microorganisms by mechanical flushing and antimicrobial action; and (4) to provide the cornea with necessary nutrient substances.
LAYERS OF THE TEAR FILM
The tear film is composed of three layers (Figure 4-16): (1) The superficial layer is a monomolecular film of lipid derived from meibomian glands. It is thought to retard evaporation and form a watertight seal when the lids are closed. (2) The middle aqueous layer is elaborated by the major and minor lacrimal glands and contains water-soluble substances (salts and proteins). (3) The deep mucinous layer is composed of glycoprotein and overlies the corneal and conjunctival epithelial cells. The epithelial cell membranes are composed of lipoproteins and are therefore relatively hydrophobic. Such a surface cannot be wetted with an aqueous solution alone. Mucin is partly adsorbed onto the corneal epithelial cell membranes and is anchored by the microvilli of the surface epithelial cells. This provides a new hydrophilic surface for the aqueous tears to spread over which is wetted by a lowering of surface tension.
COMPOSITION OF TEARS
The normal tear volume is estimated to be 7 ± 2 L in each eye. Albumin accounts for 60% of the total protein in tear fluid. Globulin and lysozymes are divided equally in the remainder. Immunoglobulins IgA, IgG, and IgE are present. IgA predominates, and differs from serum IgA in that it is not transudated from serum only but is produced by plasma cells located in the lacrimal gland. In certain allergic conditions such as vernal conjunctivitis, the IgE concentration of tear fluid increases. Tear lysozymes form 21-25% of the total protein and-acting synergistically with gamma globulins and other nonlysozyme antibacterial factors-represent an important defense mechanism against infection. Other tear enzymes may also play a role in diagnosis of certain clinical entities, eg, hexoseaminidase assay for diagnosis of Tay-Sachs disease.
K+, Na+, and Cl- occur in higher concentrations in tears than in plasma. Tears also contain a small amount of glucose (5 mg/dL) and urea (0.04 mg/dL), and changes in blood concentration parallel changes in tear glucose and urea levels. The average pH of tears is 7.35, though a wide normal variation exists (5.20-8.35). Under normal conditions, tear fluid is isotonic. Tear film osmolality ranges from 295 to 309 mosm/L.
DRY EYE SYNDROME (Keratoconjunctivitis Sicca)
Dryness of the eye may result from any disease associated with deficiency of the tear film components (aqueous, mucin, or lipid), lid surface abnormalities, or epithelial abnormalities. Although there are many forms of keratoconjunctivitis sicca, those connected with rheumatoid arthritis and other autoimmune diseases are commonly referred to as Sjögren's syndrome.
Etiology
Many of the causes of dry eye syndrome affect more than one component of the tear film or lead to ocular surface alterations that secondarily cause tear film instability. Histopathologic features include the appearance of dry spots on the corneal and conjunctival epithelium, formation of filaments, loss of conjunctival goblet cells, abnormal enlargement of nongoblet epithelial cells, increased cellular stratification, and increased keratinization. The etiology and diagnosis of keratoconjunctivitis sicca are summarized in Table 4-2.
Clinical Findings
Patients with dry eyes complain most frequently of a scratchy or sandy (foreign body) sensation. Other common symptoms are itching, excessive mucus secretion, inability to produce tears, a burning sensation, photosensitivity, redness, pain, and difficulty in moving the lids. In most patients, the most remarkable feature of the eye examination is the grossly normal appearance of the eye.The most characteristic feature on slitlamp examination is the interrupted or absent tear meniscus at the lower lid margin. Tenacious yellowish mucus strands are sometimes seen in the lower conjunctival fornix. The bulbar conjunctiva loses its normal luster and may be thickened, edematous, and hyperemic.
The corneal epithelium shows varying degrees of fine punctate stippling in the interpalpebral fissure. The damaged corneal and conjunctival epithelial cells stain with 1% rose bengal (Figure 4-17), and defects in the corneal epithelium stain with fluorescein. In the late stages of keratoconjunctivitis sicca, filaments may be seen-one end of each filament attached to the corneal epithelium and the other end moving freely (Figure 4-18).
In patients with Sjögren's syndrome, conjunctival scrapings may show increased numbers of goblet cells. Lacrimal gland enlargement occurs uncommonly in patients with Sjögren's syndrome. Diagnosis and grading of the dry eye condition can be achieved with good accuracy using the following diagnostic methods:
A. Schirmer Test:
This test is done by drying the tear film and inserting Schirmer strips (Whatman filter paper No. 41) into the lower conjunctival cul-de-sac at the junction of the mid and temporal thirds of the lower lid. The moistened exposed portion is measured 5 minutes after insertion. Less than 10 mm of wetting without anesthesia is considered abnormal.
When performed without anesthesia, the test measures the function of the main lacrimal gland, whose secretory activity is stimulated by the irritating nature of the filter paper. Schirmer tests performed after topical anesthesia (0.5% tetracaine) measure the function of the accessory lacrimal glands (the basic secretors). Less than 5 mm in 5 minutes is abnormal.
The Schirmer test is a screening test for assessment of tear production. False-positive and false-negative results occur. Low readings are sporadically found in normals, and normal tests may occur in dry eyes- especially those secondary to mucin deficiency.
B. Tear Film Break-Up Time:
Measurement of the tear film break-up time may sometimes be useful to estimate the mucin content of tear fluid. Deficiency in mucin may not affect the Schirmer test but may lead to instability of the tear film. This causes the film's rapid break-up. "Dry spots" (Figure 4-19) are formed in the tear film, and exposure of the corneal or conjunctival epithelium follows. This process ultimately damages the epithelial cells, which can then be stained with rose bengal. Damaged epithelial cells may be shed from the cornea, leaving areas susceptible to punctate staining when the corneal surface is flooded with fluorescein.
The tear film break-up time can be measured by applying a slightly moistened fluorescein strip to the bulbar conjunctiva and asking the patient to blink. The tear film is then scanned with the aid of the cobalt filter on the slitlamp while the patient refrains from blinking. The time that elapses before the first dry spot appears in the corneal fluorescein layer is the tear film break-up time. Normally, the break-up time is over 15 seconds, but it will be reduced appreciably by the use of local anesthetics, by manipulating the eye, or by holding the lids open. The break-up time is shorter in eyes with aqueous tear deficiency and is always shorter than normal in eyes with mucin deficiency.
C. Ocular Ferning Test:
A simple and inexpensive qualitative test for the study of conjunctival mucus is performed by drying conjunctival scrapings on a clean glass slide. Microscopic arborization (ferning) is observed in normal eyes. In patients with cicatrizing conjunctivitis (ocular pemphigoid, Stevens-Johnson syndrome, diffuse conjunctival cicatrization), ferning of the mucus is reduced or absent.
D. Impression Cytology:
Impression cytology is a method by which goblet cell densities on the conjunctival surface can be counted. In normal persons, the goblet cell population is highest in the infranasal quadrant. Loss of goblet cells has been documented in cases of keratoconjunctivitis sicca, trachoma, cicatricial ocular pemphigoid, Stevens-Johnson syndrome, and avitaminosis A.
E. Fluorescein Staining:
Touching the conjunctiva with a dry strip of fluorescein is a good indicator of wetness, and the tear meniscus can be seen easily. Fluorescein will stain the eroded and denuded areas as well as microscopic defects of the corneal epithelium.
F. Rose Bengal Staining:
Rose bengal is more sensitive than fluorescein. The dye will stain all desiccated nonvital epithelial cells of the cornea as well as conjunctiva
G. Tear Lysozyme Assay:
Reduction in tear lysozyme concentration usually occurs early in the course of Sjögren's syndrome and is helpful in the diagnosis of that disorder. Tears can be collected on Schirmer strips and assayed. The most common method is spectrophotometric assay
H. Tear Osmolality:
Hyperosmolality of tears has been documented in keratoconjunctivitis sicca and in contact lens wearers and is thought to be a consequence of decreased corneal sensitivity. Reports claim that hyperosmolality is the most specific test for keratoconjunctivitis sicca. It can occur even with a normal Schirmer test and normal rose bengal staining
I. Lactoferrin:
Tear fluid lactoferrin is low in patients with hyposecretion of the lacrimal gland. Testing kits are commercially available.
Complications
Early in the course of keratoconjunctivitis sicca, vision is slightly impaired. As the condition worsens, discomfort can become disabling. In advanced cases, corneal ulceration, corneal thinning, and perforation may develop. Secondary bacterial infection occasionally occurs, and corneal scarring and vascularization may result in marked reduction in vision. Early treatment may prevent these complications.
Treatment
The patient should understand that dry eyes is a chronic condition and complete relief is unlikely except in mild cases when the corneal and conjunctival epithelial changes are reversible. Artificial tears are the mainstay of treatment. Ointment is useful for prolonged lubrication, especially when sleeping. Additional relief can be achieved by using humidifiers, moisture chamber spectacles, or swim goggles.
The primary function of these measures is fluid replacement. Restoration of mucin is a more formidable task. In recent years, high-molecular-weight water-soluble polymers have been added to artificial tears in an attempt to improve and prolong surface wetting. Other mucomimetic agents include sodium hyal- uronate and solutions of the patient's own serum as eye drops. If the mucus is tenacious, as in Sjögren's syndrome, mucolytic agents (eg, acetylcysteine 10%) are helpful.
Patients with excessive tear lipids require specific instructions for removal of lipid from the eyelid margin. Antibiotics topically or systemically may be necessary. Topical vitamin A may be useful in reversing ocular surface metaplasia.
All chemical preservatives in artificial tears induce a certain amount of corneal toxicity. Benzalkonium chloride is the most damaging of the commonly used preparations. Patients who require frequent drops fare better with nonpreserved solutions. Preservatives can also cause idiosyncratic reactions. This is most common with thimerosal.
Patients with dry eyes from any cause are more likely to have concurrent infections. Chronic blepha-ritis is common and should be treated with hygiene and topical antibiotics. Acne rosacea is associated with keratoconjunctivitis sicca, and treatment with systemic tetracycline may be helpful.
Surgical treatment for dry eyes includes insertion of temporary (collagen) or extended (silicone) punctal plugs to retain lacrimal secretions. Permanent closure of the puncta and canaliculi can be done by thermal, electrocautery, or laser treatment.
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10.1036/1535-8860.ch4