1 Comment

Chapter 65 – Dry Eye

Chapter 65 – Dry Eye










• Dry eye syndrome is a clinical condition characterized by deficient tear production or excessive tear evaporation resulting in ocular discomfort.



• Ocular irritation.

• Conjunctival injection.

• Ocular surface disruption.



• Possible autoimmune disease.

• Possible conjunctival or lid abnormalities.

• Systemic and topical medications.

• Blurred or unstable vision.





Dry eye syndrome (DES) is characterized by ocular irritation resulting from an alteration of the tear film. The effects of DES can vary from minor inconvenience for most sufferers to rare sight-threatening complications in severe cases. Although the diagnosis of DES has traditionally focused on inadequate secretion, or aqueous tear deficiency, the tear film is a complex and delicately balanced unit dependent on the normal function of several distinct components.[1] [2] Both systemic and local conditions can affect these individual components, and these conditions can be identified through a detailed history and examination.

Current treatment is heavily weighted toward supplementation, stimulation, or preservation of aqueous tears, which is satisfactory for most patients. DES, however, often involves multiple deficiency states that, when disregarded, can result in treatment failure and frustration for both the patient and the physician. A more thorough understanding of DES and its interaction with the ocular surface is leading to promising and more complete approaches to treatment.


Normal Physiology

The tear film is composed of mucin, aqueous, and lipid components stratified into distinct layers in the resting tear film. The mucin layer consists of high–molecular-weight glycoproteins that adhere to surface epithelium and its secreted glycocalyx. This mucinous coating of the hydrophobic epithelial cell surface provides a level, hydrophilic surface,[3] permitting smooth distribution of the overlying aqueous layer. Although recent studies have demonstrated mucin secretion by squamous epithelial cells of the cornea and conjunctiva,[4] its primary source is conjunctival goblet cells. The aqueous layer is approximately 70?µm thick and constitutes the largest volume of the tear film. In an undisturbed state, it rests above the mucin but deep to the lipid layer. The aqueous is secreted by the main lacrimal gland and accessory glands of Krause and Wolfring, with a small contribution from conjunctival vessels and the cornea. As the name implies, the aqueous layer consists primarily of water but also contains electrolytes (Na, K, Cl) and myriad proteins, including epidermal growth factor, immunoglobulins (IgA, IgG, IgM), lactoferrin, lysozyme, and other cytokines.[5] [6] The precise role of these proteins is unknown, but they likely play both a protective and a homeostatic role for the ocular surface. Last, meibomian glands secrete the lipid layer, which contains chiefly sterol esters and wax monoesters.[7] [8] Although only 0.1?µm thick, the lipid layer serves to stabilize the tear film by increasing surface tension and retarding evaporation.

The tear layer has a variety of different functions, including maintenance of a smooth surface for optical clarity, lubrication to facilitate eyelid blink, and protection against ocular infection.[1] Average tear flow is about 1.2?µm/min.[9] Blinking serves to periodically distribute tears evenly over the ocular surface and promotes the constant turnover of tears by encouraging both secretion and mechanical drainage of tears through the lacrimal drainage system. Regulation of secretion is not completely understood, but it appears to involve both neuronal and hormonal pathways. Direct innervation of the lacrimal gland, meibomian glands, and goblet cells has been demonstrated, with M3 class cholinergic receptors predominating in the lacrimal gland.[10] The effect of hormonal triggers is less clear, but androgens appear to have a positive effect on the secretion of both aqueous and lipid tears.[11] [12]

The tear film and ocular surface form a highly interdependent complex. Deficiencies of the tear film lead to either hyperosmolar toxicity or direct exposure of the cornea and conjunctiva; persistent DES leads to reactive structural and cellular changes of the ocular surface.[13] Squamous metaplasia of the conjunctiva and cornea, corneal epitheliopathy, and filamentary keratitis can all be associated with chronic low tear volume.

Classification of Dry Eye

The National Eye Institute/Industry Workshop adopted the following definition of dry eye[14] : Dry eye is a disorder of the tear film due to tear deficiency or excessive tear evaporation which causes damage to the interpalpebral ocular surface and is associated with symptoms of ocular discomfort. This definition encompasses all the clinical entities associated with systemic disease, as well as idiopathic dry eye disease. As a result of these workshops, a classification system algorithm for dry eye was produced ( Fig. 65-1 ).


Defective lacrimal function as a cause of dry eye subdivides into two categories: non–Sjögren’s tear deficiency (NSTD), and Sjögren’s syndrome tear deficiency (SSTD). NSTD has no association with systemic autoimmune disease, which is a cardinal feature of SSTD. The description of keratoconjunctivitis sicca (KCS) that Sjögren[15] gave in his 1933 article has become associated with his name. The term KCS–Sjögren’s syndrome is used in much of the world literature for the ocular surface disease that occurs in Sjögren’s syndrome,





Figure 65-1 Dry eye classification. (With permission from Lemp MA. The 1998 Castroviejo lecture. New strategies in the treatment of dry-eye states. Cornea. 1999;18[6]:625–32.)

whereas the term non–Sjögren’s syndrome KCS is used for primary, age-related tear deficiency.

Non–Sjögren’s Tear Deficiency.

NSTD can occur from impaired glandular production, impaired afferent or efferent stimulation, or local ocular surface disease. Primary lacrimal deficiency may result from congenital alacrima, a rare condition of children born with absent or hypoplastic lacrimal glands. Another inborn disease, Riley-Day syndrome, features aberrant parasympathetic innervation in a functional lacrimal gland with intact reflex tearing. The large majority of patients who have DES, however, are categorized as having acquired lacrimal gland deficiency, primary lacrimal deficiency, or idiopathic KCS syndrome. The pathogenesis is unknown, but DES may result from either age-related changes in the lacrimal gland[16] or an immune mechanism evidenced by round cell infiltration of the lacrimal gland and ductal tissue.[17]

Secondary lacrimal deficiency can result from infiltration of the lacrimal gland. Lymphoma, sarcoidosis, hemochromatosis, amyloidosis, human immunodeficiency virus infection, and graft-versus-host disease all can result in dry eye from this process.[18] [19] Similarly, surgical or radiation-induced destruction of lacrimal tissue can result in severe dry eye.

Systemic medications are a common source for the inhibition of efferent lacrimal gland stimulation. Numerous medications are associated with DES ( Table 65-1 ), many of which reduce lacrimation through either anticholinergic inhibition of the lacrimal gland or systemic dehydration.[20] Mechanical trauma to efferent secretomotor fibers to the lacrimal gland also may result in dry eye.[18]

DES has been reported in association with menopause.[21] Although most systemic symptoms of menopause are related to decreasing levels of estrogen, supplementation studies have not shown a beneficial effect in DES.[22] The cause of postmenopausal DES, therefore, is hypothesized to be due to alterations in other hormones, especially androgens, which are also reduced during menopause.

Interruption of the afferent stimulus of tear production, or sensory loss (denervation), results in decreased tear secretion and reduced blink rate. Tear flow decreases by 60–75%, and blink rate decreases by 30% after topical instillation of anesthetic.[23] [24] Damage to afferent sensory fibers resulting in dry eye has been reported after incisional surgery of the cornea (penetrating keratoplasty, radial keratotomy, and limbal cataract incision) and after damage to the first division of the trigeminal ganglion from trauma, tumor, herpes simplex, or zoster. Physiologically, denervation also results in corneal epithelial atrophy, compounding the risk of corneal ulceration.

LASIK and photorefractive keratectomy are increasingly recognized as precipitating causes of dry eye.[25] Postsurgical findings of decreased corneal sensation, tear production, and blink rate lasting 6–18 months or more are evidence of neurotrophic DES. [26] [27] [28] The incidence may be higher in LASIK because the incision involves 270° of the corneal circumference, severing penetrating branches of the long ciliary nerves. [25] Donnenfeld et al.[29] reported significantly greater dry eye in patients with superior hinge placement, suggesting that nasal hinge placement may preserve a greater number of these nerve branches. The resultant contour of the corneal surface may also prevent proper tear distribution. Avoidance of surgery, especially LASIK, in patients at risk for corneal neuropathy (i.e., those with advanced diabetes or preexisting severe dry eye) is strongly recommended.

Sjögren’s Syndrome Tear Deficiency.

Sjögren’s syndrome is a clinical condition of aqueous tear deficiency combined with dry mouth. The syndrome is classified as primary—patients without a defined connective tissue disease—and secondary—patients who have a confirmed connective tissue disease, most often rheumatoid arthritis. Secondary SSTD is also associated with systemic lupus erythematosus, polyarteritis, Wegener’s granulomatosis, scleroderma, polymyositis, dermatomyositis, and primary biliary cirrhosis. All feature progressive lymphocytic infiltration of the lacrimal and salivary glands and can be associated with severe and painful ocular and oral discomfort. The pathogenesis of the tear deficit in SSTD is infiltration of the lacrimal gland by B and CD4 lymphocytes (with some CD8 lymphocytes) and by plasma cells, with subsequent fibrosis. Fox[19] laid out criteria to establish the diagnosis of Sjögren’s syndrome:

• Abnormally low Schirmer’s test result.

• Objectively decreased salivary gland flow.



• Biopsy-proved infiltration of the labial salivary glands.

• Serum autoantibodies (antinuclear antibody, rheumatoid factor, or the specific antibodies anti-Ro [SS-A] and anti-La [SS-B]).




Mechanism of Action





Tolterodine tartrate (Detrol)



Antihistamines (sedating compounds are associated with greater dryness)

Chlorpheniramine (Chlor-Trimeton)

Diphenhydramine (Benadryl)

Promethazine (Phenergan)



MAO inhibitors

Amitriptyline (Elavil)

Nortriptyline (Pamelor)

Imipramine (Tofranil)




Chlorpromazine (Thorazine)

Thioridazine (Mellaril)

Fluphenazine (Prolixin)






Disopyramide (Norpace)


Alpha agonists

Clonidine (Catapres)

Methyldopa (Aldomet)


Beta blockers

Propranolol (Inderal)

Metoprolol (Lopressor)






Ibuprofen (Advil)

Naproxen (Naprosyn, Aleve)






When all four factors are present, a definite diagnosis of Sjögren’s syndrome is made; if three of the four are met, a provisional diagnosis can be made.


Excessive evaporation that occurs in specific periocular disorders can cause dry eye disease with or without concurrent aqueous tear deficiency. Evaporation leads to both loss of tear volume and a disproportionate loss of water, resulting in hyperosmolarity. Environmental conditions such as high altitude, dryness, or extreme heat accelerate tear loss even in normal individuals.

Meibomian Gland Disease and Blepharitis.

Meibomian gland dysfunction (MGD) leads to both decreased secretion and abnormal composition of the tear film lipid layer. The meibomian gland secretions (meibum) are altered in MGD, leading to meibomian gland blockage as well as reducing its effectiveness in the tear film. The abnormal lipids cause both ocular surface and eyelid inflammation, perpetuating a cycle of inflammation, scarring, hyperkeratosis, stenosis, and further MGD. The resultant lipid layer is unable to maintain stability of the tear film and retard evaporation.

MGD is associated with abnormal bacterial colonization, acne rosacea, and seborrheic dermatitis. Abnormal bacterial colonization may act directly by altering secreted lipids or indirectly by causing inflammation. Acne rosacea is a dermatological disorder resulting in vascular dilatation, telangiectasias, and plugging of sebaceous glands of both facial and eyelid skin.


Excessive exposure of the ocular surface leads to increased evaporative loss of tears; thus, any disorder that results in increased ocular exposure can cause evaporative dry eye. Trauma to the eyelid, whether mechanical or neurological, that results in impaired or reduced blinking, lagophthalmos, or an increased palpebral fissure width can result in an evaporative dry eye. Evaporative dry eye can be seen in thyroid eye disease secondary to proptosis or lid retraction. Comatose patients and some psychiatric patients may have central nervous system–induced exposure from an impaired blink reflex.

Mucin Deficiency.

Local ocular surface disorders such as cicatrizing diseases of the conjunctiva or surgical trauma may result in aqueous tear deficiency by scarring of the tear ducts. More important, these processes destroy mucin-producing goblet cells and cause anatomical abnormalities of the conjunctiva, preventing proper tear distribution. Although uncommon in incidence, trachoma, mucous membrane pemphigoid, Stevens-Johnson syndrome, and chemical and thermal burns can result in severe DES not amenable to aqueous tear replacement therapy. Vitamin A deficiency similarly can result in extensive goblet cell loss and squamous metaplasia.[30]


Most forms of dry eye have symptoms, interpalpebral surface damage, tear instability, and tear hyperosmolarity. Many symptoms of DES are the same, regardless of cause. Typical complaints include burning, itching, foreign body sensation, stinging, dryness, photophobia, ocular fatigue, and redness. Although symptoms are usually nonspecific, careful attention to a patient’s complaints will help refine the diagnosis.

Patients commonly describe a diurnal pattern. Aqueous tear deficiency typically presents with worsening symptoms over the day and decompensation in particular environmental conditions. Low humidity in airline cabins and in modern office buildings with climate control can be exacerbating factors for the development of symptomatic DES.[31] Video display terminals have been associated with both decreased blink rate and increased tear evaporation, which can contribute to dry eye.[32] Conversely, nighttime exposure, floppy eyelid syndrome, and inflammatory conditions often present with discomfort on awakening and improvement over the day.

Patients with an unstable tear film report intermittent visual blurring and discomfort. A gritty or sandy sensation is common in meibomian gland disease. It is important to recognize that diabetic patients and patients with other corneal neuropathies may exhibit signs of DES with or without discomfort. Recognition of corneal neurosensory loss is critical in determining the course of therapy and observation, since these patients are at high risk for keratolysis.

Common signs of DES include conjunctival injection, decreased tear meniscus, photophobia, increased tear debris, and loss of corneal sheen. Findings are more common in the exposed interpalpebral fissure. DES patients may experience excess





Figure 65-2 Seventy-three-year-old patient with rheumatoid arthritis and secondary Sjögren’s syndrome.

tearing or even epiphora as a result of reflex tearing. DES patients are also at greater risk for external infections secondary to decreased tear turnover and desiccation of the surface epithelium. Instability of the surface epithelium and disordered mucin production may lead to painful and recurrent filamentary keratitis. Keratinization may occur in chronic DES, but vitamin A deficiency should also be suspected. Meibomian gland inspissation, telangiectasias, glandular dropout (seen on transillumination of the tarsus), chalazions, and eyelash debris are found in meibomian gland disease and blepharitis.

Patients who have SSTD tend to have more severe symptoms and more serious findings than do NSTD patients. Sterile ulceration may be seen in SSTD. Ulceration of the cornea can be peripheral or paracentral; both thinning and perforation of these ulcers can occur. Figure 65-2 shows a patient with paracentral ulceration secondary to SSTD. Acute lacrimal enlargement may be seen in SSTD but should be differentiated from Mikulicz’s disease, which results from infiltration of the gland without surface findings.[33]

The result of DES is hyperosmolar toxicity and exposure of the underlying ocular surface. Chronically present, this leads to a loss of conjunctival goblet cells, epithelial cell dysfunction, and, in advanced cases, metaplasia and keratinization. These changes manifest as “dry” patches and keratinization of the conjunctiva. Disruption of the normal epithelial barrier promotes release of the pro-inflammatory cytokines interleukin-1, interleukin-6, interleukin-8, and tumor necrosis factor, among others, leading to further epithelial damage. The cornea exhibits similar changes, with disruption of tight junctions and abnormal epithelial-mucin interaction.


Diagnostic Dye Evaluation

Fluorescein is a large molecule that is normally unable to traverse the tight junctions of an intact epithelium. These tight junctions in advanced DES are disrupted, producing characteristic diffuse subepithelial or punctate staining. Rose bengal, a derivative of fluorescein, is used to detect ocular surface damage by staining devitalized epithelial cells. Feenstra and Tseng[34] showed that rose bengal stains healthy epithelial cells if a normal amount of mucin does not overlie the cell surface. Since 1% rose bengal solution is no longer commercially available, impregnated strips wetted with artificial tears may be used. Proparacaine should be avoided because it dilutes rose bengal poorly and may desiccate the ocular surface, creating spurious results.



Figure 65-3 Modified van Bijsterveld conjunctival rose bengal grading map. The density of rose bengal staining is recorded on a scale of 0–3 for each of six areas of the conjunctiva, and then summed for each eye. (With permission from Lemp MA. The 1998 Castroviejo lecture. New strategies in the treatment of dry-eye states. Cornea. 1999;18[6]:625–32.)



Figure 65-4 Dry eye syndrome with rose bengal staining.

Van Bijsterveld[35] created a grading scale for rose bengal dye that divides the ocular surface into three zones: nasal bulbar conjunctiva, cornea, and temporal bulbar conjunctiva. Each zone is evaluated for density of stain in the range 0–3 (0, none; 3, confluent staining). An additive zone stain total of 3.5 or more in the eye constitutes a positive test for dry eye. Typically, the conjunctiva stains to a greater extent than the cornea, and the nasal conjunctiva shows more stain than the temporal.[16] Lemp and the National Eye Institute/Industry Workshop group[14] suggest that the conjunctiva be divided into six areas and graded in a similar manner ( Fig. 65-3 ). Figure 65-4 is a clinical example of an eye with KCS stained with rose bengal. Also widely available, lissamine green does not irritate the eye and stains for cell death or degeneration, as well as cell-to-cell junction disruption.[36]

Tear Film Stability

Tear film instability may be a result of either tear deficiency or evaporative DES. One of the common objective tests used to help make a diagnosis of dry eye is tear breakup time (TBUT), described by Norn and revised by Lemp and Holly.[37] Tears are stained with fluorescein dye, and the time interval is measured between a complete blink to the first appearance of a dry spot in the precorneal tear film. Theoretically, TBUTs shorter than the blink interval of 5 seconds could result in surface damage, and very short TBUTs (less than 2 seconds) indicate KCS.



Unfortunately, results are skewed by the introduction of a fluorescein-saline mixture into the tear film, iatrogenically reducing its stability, especially if the saline is preserved. A noninvasive measure developed by Mengher et al.[38] to assess tear film stability is the Xeroscope, which projects a lighted grid pattern onto the tear surface. Interestingly, tear film stability tested in this fashion measured about 40 seconds in normal subjects, whereas in dry eye patients, tear film stability survived for about 12 seconds (exceeding the aforementioned 5-second blink interval). Nonetheless, TBUT is a useful clinical tool for evaluating DES.

Measurement of Tear Production

For years, the most common means of measuring tear production has been Schirmer’s test, the details of which were first published in 1903. [39] Much disagreement exists as to the validity and usefulness of Schirmer’s test. Jones[40] advocated the use of topical anesthesia combined with a Schirmer’s test strip for 5 minutes to reduce the effect of the presence of the filter paper strip; this has become the “basal” test. False-negative and false-positive results cloud the usefulness of each test. The application of Schirmer’s test is fraught with inconsistencies that limit its repeatability in DES,[41] but it still enjoys widespread use. With these caveats in mind, the following general guidelines are recommended:

• A 5-minute test that results in less than 5?mm of wetting confirms the clinical diagnosis of DES.

• A result of 6–10?mm of wetting suggests a dry eye problem.

Hamano et al.[42] developed the phenol red thread test in an attempt to overcome some of the disadvantages of Schirmer’s test. In this test, 3?mm of dye-impregnated 75?mm cotton thread is placed under the lateral one fifth of the inferior palpebral lid margin; it is allowed to absorb tears for 15 seconds—its color changes to bright orange from tear contact (as a result of the slightly alkaline pH of tears). The patient has little awareness of the thread, which eliminates the need for anesthesia. There seems to be a racially biased variation of response, with Asian populations showing a lessened wet-length response; these differences diminish with advancing age.[43] Direct stimulation of the nasociliary nerve through irritation of the nasopharynx confirms the presence or absence of reflex tearing.

Although it is clear that tears in dry-eye patients generally have a higher osmolarity than normal and that measurement of tear osmolarity provides a sensitive test, it is not specific, standardized, or readily attainable. Also, the degree of tear osmolarity does not distinguish between tear-deficient and tear-sufficient dry eye, as the increased evaporation in the latter also results in hyperosmolar tears. Other tests for reduced tear function include fluorophotometry for decreased protein content, lysozyme levels, ocular ferning, impression cytology, and lactoferrin assays. None of these tests enjoys widespread use in clinical settings.

Other Tests

Corneal sensation may be qualitatively assessed with a cotton wisp, but quantification requires an instrument such as the Cochet-Bonnet aesthesiometer, a subjective test using a thin standardized wisp of varying length. More predictive than Schirmer’s test, the tear clearance test measures tear turnover with serial tear collection after instillation of a standardized volume of dye.[41] [44] Serological tests, including antinuclear, anti-Ro, and anti-La antibodies, should be performed in patients suspected of having autoimmune DES. A definitive diagnosis of Sjögren’s syndrome requires, however, minor salivary or, rarely, lacrimal gland biopsy.


Neither clinical presentation nor individual ancillary tests alone are sufficient for an accurate diagnosis of DES. Because of the therapeutic importance of appropriate categorization of patients, Pflugfelder et al. [45] combined standard subjective examination with ancillary tests in the evaluation of SSTD, NSTD, inflammatory MGD, and atrophic MGD patients. Clinically important results were identified and compiled into an algorithm that helps differentiate DES patients with available tests ( Fig. 65-5 ).



Figure 65-5 Diagnostic algorithm for ocular irritation. (With permission from Pflugfelder SC, Tseng SC, Sanabria O, et al. Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorders known to cause ocular irritation. Cornea. 1998;17[1]:38–56.)




Significant advances have been made in treating the many facets of dry eye, but it remains a disorder of long-term maintenance rather than permanent cure. Current therapy focuses on tear supplementation to allow resident healing mechanisms to restore a normal ocular surface. Chronic DES, however, induces aberrant inflammatory and cellular changes that impede healing. Evolving therapeutic approaches are directed toward modulation of these aberrant processes as well as promotion of normal tear secretion. Since the tear film is a highly integrated unit, optimizing each layer, regardless of how minor the abnormality, is central to the successful treatment of DES.

Aqueous Tear Deficiency

As the first line of treatment, artificial tears both increase available tears and lower tear osmolarity through dilutional effects. A large number of artificial tears are available commercially, differing in electrolyte composition and preservative. The addition of “thickening” agents such as methylcellulose, hydroxypropyl methylcellulose, and polyvinyl alcohol can prolong retention of the tears on the ocular surface. Physiological buffering and hypotonicity may be beneficial to the ocular surface and decrease hyperosmolarity further. The compatibility of a tear preparation is highly dependent on an individual patient’s preferences, which may involve such disparate concerns as cost, comfort, visual blurring, and ease of delivery. It is clear, however, that the use of traditionally preserved tears in moderate or severe dry eye is poorly tolerated and harmful. For patients with significant dry eye, single-dose, nonpreserved tear preparations are the mainstay of therapy. Because of the cost, inconvenience, and difficulty in handling the vials, bottled tear products utilizing sodium perborate or a stabilized oxychloro complex are a reasonable alternative. These preservatives have good antimicrobial activity but are converted to harmless compounds when in contact with the ocular surface. Artificial tear ointments can be effective for longer-lasting control of symptoms, but visual blurring limits their usefulness for many patients. They are most effective in balancing decreased tear production and exposure in the nighttime hours.

Secretagogues are agents that stimulate lacrimal gland secretion and increase available tears, requiring functional glandular tissue. Oral pilocarpine (Salagen) and cevimeline (Evoxac) are two M3 cholinergic agonists approved for use in dry mouth that also stimulate tear secretion.[10] [46] The effect tends to be greater in oral dryness than in dry eye, and systemic cholinergic side effects may limit their use. Buccal salivary gland transplantation and parotid duct transposition have been largely abandoned but may have utility in specific cases. [47] Various nutritional supplements are also touted for DES but without scientific confirmation of their safety or efficacy. Punctal occlusion retards tear drainage, thereby increasing tear volume on the ocular surface and lowering tear osmolarity. Occlusion may be achieved irreversibly by cauterization or reversibly with the use of various silicone plugs. YAG laser occlusion is characterized by a high incidence of recanalization. The use of collagen or 5-0 chromic gut for temporary occlusion can help identify those borderline patients at risk for epiphora prior to permanent occlusion. It should be noted that epiphora in the presence of one functional punctum in patients with little or no tear production is uncommon.


Evaporative Dry Eye

Primary treatment of tear evaporation involves stabilizing the lipid tear layer. Since lipid tear substitutes are investigational and not widely available, treatment is focused on improving the quality and quantity of native meibomian gland secretions. Lid hygiene, in the form of warm compresses and lid massage, is effective in improving meibomian gland secretion. Lid scrubs with dilute detergents can decrease seborrheic or bacterial load, helping to break the pro-inflammatory cycle of MGD. The addition of a systemic tetracycline has also been shown to decrease local inflammation and improve meibomian gland function, resulting in improved patient comfort. Treatment must continue for several weeks to see an effect.

Correction of eyelid abnormalities that increase exposure of the ocular surface, such as lower lid ptosis and lagophthalmos, can stabilize a decompensated ocular surface. In severe cases, a partial or complete tarsorrhaphy or a conjunctival flap may be necessary to prevent complete decompensation of the cornea. The use of humidifiers, moist chambers, glasses, or goggles decreases evaporative pressure. New high-Dk, high-water-content contact lenses and new polymer lenses, accompanied by proper tear supplementation and hygiene, are effective in treating DES patients with poor corneal wetting.

Ocular Surface Inflammation

Treating the secondary inflammatory response and consequential cellular changes of dry eye is more controversial. DES-induced ocular surface inflammation disrupts the epithelial and mucin layers, further exacerbating tear film breakdown. Persistent inflammation can prevent effective treatment of either aqueous or lipid tear deficiency. Immune modulators such as corticosteroids, cyclosporine A, and tetracyclines have all been used with some success in reversing the destructive effects of KCS. [47] [48] [49] Control of these reactive epithelial changes has been shown to restore normal cell morphology, cell-to-cell interactions, and critical mucin production and clearly has a role in the treatment at all forms of DES. A better understanding of surface inflammation and the development of specific agents are needed to prevent and reverse the structural changes induced by dry eye.





1. Rolando M, Zierhut M. The ocular surface and tear film and their dysfunction in dry eye disease. Surv Ophthalmol. 2001;45(Suppl 2):S203–10.


2. Tseng SC, Tsubota K. Important concepts for treating ocular surface and tear disorders. Am J Ophthalmol. 1997;124(6):825–35.


3. Argueso P, Gipson IK. Epithelial mucins of the ocular surface: structure, biosynthesis and function. Exp Eye Res. 2001;73(3):281–9.


4. Watanabe H, Fabricant M, Tisdale AS, et al. Human corneal and conjunctival epithelia produce a mucin-like glycoprotein for the apical surface. Invest Ophthalmol Vis Sci. 1995;36(2):337–44.


5. Barton K, Nava A, Monroy DC, Pflugfelder SC. Cytokines and tear function in ocular surface disease. Adv Exp Med Biol. 1998;438:461–9.


6. Solomon A, Dursun D, Liu Z, et al. Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease. Invest Ophthalmol Vis Sci. 2001;42(10):2283–92.


7. Driver PJ, Lemp MA. Meibomian gland dysfunction. Surv Ophthalmol. 1996;40(5):343–67.


8. Bron AJ, Tiffany JM. The meibomian glands and tear film lipids. Structure, function, and control. Adv Exp Med Biol. 1998;438:281–95.


9. Mishima S, Gasset A, Klyce SD Jr, Baum JL. Determination of tear volume and tear flow. Invest Ophthalmol. 1966;5(3):264–76.


10. Fox RI, Michelson P. Approaches to the treatment of Sjogren’s syndrome. J Rheumatol Suppl. 2000;61:15–21.


11. Krenzer KL, Dana MR, Ullman MD, et al. Effect of androgen deficiency on the human meibomian gland and ocular surface. J Clin Endocrinol Metab. 2000;85(12):4874–82.


12. Lemp MA. The 1998 Castroviejo lecture. New strategies in the treatment of dry-eye states. Cornea. 1999;18(6):625–32.


13. Stern ME, Beuerman RW, Fox RI, et al. The pathology of dry eye: the interaction between the ocular surface and lacrimal glands. Cornea. 1998;17(6):584–9.


14. Lemp MA. Report of the National Eye Institute/Industry Workshop on Clinical Trials in Dry Eyes. CLAO J. 1995;21(4):221–32.


15. Sjögren H. Zur kenntnis der keratoconjunctivitis sicca (Keratitis filiformis bei hypofunktion der tranendrusen). Acta Ophthalmol (Copenh). 1933;2:1–151.


16. Obata H, Yamamoto S, Horiuchi H, Machinami R. Histopathologic study of human lacrimal gland. Statistical analysis with special reference to aging. Ophthalmology. 1995;102(4):678–86.


17. Nasu M, Matsubara O, Yamamoto H. Post-mortem prevalence of lymphocytic infiltration of the lacrimal gland: a comparative study in autoimmune and non-autoimmune diseases. J Pathol. 1984;143(1):11–5.


18. Gilbard J, ed. Dry eye disorders. In: Albert JF, ed. Principles and practice of ophthalmology. Philadelphia: WB Saunders; 1994:257–76.


19. Fox RI. Systemic diseases associated with dry eye. Int Ophthalmol Clin. 1994; 34(1):71–87.


20. Fraunfelder F, Fraunfelder FW. Drug-induced ocular side effects, 5th ed. Boston: Butterworth-Heinemann; 2001.


21. Mathers WD, Stovall D, Lane JA, et al. Menopause and tear function: the influence of prolactin and sex hormones on human tear production. Cornea. 1998;17(4):353–8.





22. Schaumberg DA, Buring JE, Sullivan DA, Dana MR. Hormone replacement therapy and dry eye syndrome. JAMA. 2001;286(17):2114–9.


23. Jordan A, Baum J. Basic tear flow. Does it exist? Ophthalmology. 1980;87(9): 920–30.


24. Collins M, Seeto R, Campbell L, Ross M. Blinking and corneal sensitivity. Acta Ophthalmol. 1989;67(5):525–31.


25. Ang RT, Dartt DA, Tsubota K. Dry eye after refractive surgery. Curr Opin Ophthalmol. 2001;12(4):318–22.


26. Battat L, Macri A, Dursun D, Pflugfelder SC. Effects of laser in situ keratomileusis on tear production, clearance, and the ocular surface. Ophthalmology. 2001;108(7):1230–5.


27. Wilson SE. Laser in situ keratomileusis–induced (presumed) neurotrophic epitheliopathy. Ophthalmology. 2001;108(6):1082–7.


28. Benitez-del-Castillo JM, del Rio T, Iradier T, et al. Decrease in tear secretion and corneal sensitivity after laser in situ keratomileusis. Cornea. 2001;20(1):30–2.


29. Donnenfeld ED, Perry HD, Ehrenhaus M, et al. The effect of hinge position on corneal sensation and dry eye signs and symptoms. New Orleans: 2001, American Academy of Ophthalmology.


30. Smith J, Steinemann TL. Vitamin A deficiency and the eye. Int Ophthalmol Clin. 2000;40(4):83–91.


31. Sommer HJ, Johnen J, Schongen P, Stolze HH. Adaptation of the tear film to work in air-conditioned rooms (office-eye syndrome). German J Ophthalmol. 1994;3(6):406–8.


32. Tsubota K, Nakamori K. Dry eyes and video display terminals. N Engl J Med. 1993;328(8):584.


33. Tsubota K, Fujita H, Tsuzaka K, Takeuchi T. Mikulicz’s disease and Sjogren’s syndrome. Invest Ophthalmol Vis Sci. 2000;41(7):1666–73.


34. Feenstra RP, Tseng SC. Comparison of fluorescein and rose bengal staining. Ophthalmology. 1992;99(4):605–17.


35. van Bijsterveld OP. Diagnostic tests in the sicca syndrome. Arch Ophthal. 1969; 82(1):10–4.


36. Norn MS. Lissamine green. Vital staining of cornea and conjunctiva. Acta Ophthalmol. 1973;51(4):483–91.


37. Lemp MA, Holly FJ. Recent advances in ocular surface chemistry. Am J Optom Arch Am Acad Optom. 1970;47(9):669–72.


38. Mengher LS, Bron AJ, Tonge SR, Gilbert DJ. A non-invasive instrument for clinical assessment of the pre-corneal tear film stability. Curr Eye Res. 1985;4(1):1–7.


39. Schirmer O. Studien zur Physiologie und Pathologie der Tranenabsonderung und Tranenabfuhr. Albrecht von Graefes Arch Ophthalmol. 1903;56:197–291.


40. Jones LT. The lacrimal secretory system and its treatment. J All India Ophthalmol Soc. 1966;14(5):191–6.


41. Afonso AA, Monroy D, Stern ME, et al. Correlation of tear fluorescein clearance and Schirmer test scores with ocular irritation symptoms. Ophthalmology. 1999;106(4):803–10.


42. Hamano T, Mitsunaga S, Kotani S, et al. Tear volume in relation to contact lens wear and age. CLAO J. 1990;16(1):57–61.


43. Sakamoto R, Bennett ES, Henry VA, et al. The phenol red thread tear test: a cross-cultural study. Invest Ophthalmol Vis Sci. 1993;34(13):3510–4.


44. Macri A, Pflugfelder S. Correlation of the Schirmer 1 and fluorescein clearance tests with the severity of corneal epithelial and eyelid disease. Arch Ophthalmol. 2000;118(12):1632–8.


45. Pflugfelder SC, Tseng SC, Sanabria O, et al. Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorders known to cause ocular irritation. Cornea. 1998;17(1):38–56.


46. Vivino FB, Al-Hashimi I, Khan Z, et al. Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjogren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group. Arch Intern Med. 1999;159(2):174–81.


47. Sieg P, Geerling G, Kosmehl H, et al. Microvascular submandibular gland transfer for severe cases of keratoconjunctivitis sicca. Plast Reconstr Surg. 2000; 106(3):554–60; discussion 561–2.


48. Marsh P, Pflugfelder SC. Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjogren syndrome. Ophthalmology. 1999;106(4): 811–6.


49. Kunert KS, Tisdale AS, Stern ME, et al. Analysis of topical cyclosporine treatment of patients with dry eye syndrome: effect on conjunctival lymphocytes. Arch Ophthalmol. 2000;118(11):1489–96.

One comment on “Chapter 65 – Dry Eye

  1. […] Chapter 65 – Dry Eye | Free Medical TextbookDec 29, 2010 … Meibomian gland inspissation, telangiectasias, glandular dropout (seen on transillumination of the tarsus), chalazions, and eyelash debris … Leave a comment « Sport dinnerware Comments are closed. […]

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: