Figure 3-11 Filamentary keratopathy in a vascularized cornea. (Courtesy of Minas T. Coroneo, MD.)

Table 3-4

Evaporative Dry Eye

The symptoms in evaporative dry eye consist of burning, foreign-body sensation, redness of the

eyelids and conjunctiva, and filmy vision that is worse in the morning. The clinical signs associated with evaporative disease are usually confined to the posterior eyelid margins, although patients may occasionally have associated seborrheic changes on the anterior eyelid margin. The posterior eyelid margins are often irregular and have prominent, telangiectatic blood vessels (brush marks) coursing from the posterior to anterior eyelid margins. The meibomian gland orifices may pout or show metaplasia, with a white plug of keratin protein extending through the glandular orifice (Fig 3-12). They also may become posteriorly displaced on the eyelid margin. In active disease, meibomian secretions may be turbid and more viscous.

Figure 3-12 Meibomian gland dysfunction.

Recently, the term nonobvious obstructive MGD was coined to describe cases in which the patient is symptomatic but lacks obvious clinical signs of meibomian disease. The meibomian glands appear normal; however, with mild compression the glands are found to be obstructed. More forceful expression produces a thin filamentous secretion due to narrowing of the distal portion of the ducts, near the orifice. This condition is believed to be a precursor to clinically apparent disease. Expression of the glands can be performed using a cotton swab or a commercially available handheld device.

Extensive atrophy of the meibomian gland acini may develop after years of inflammation from MGD, so that eyelid compression does not produce expression of meibomian gland secretions. Atrophy of meibomian gland acini and derangement of glandular architecture can be demonstrated by shortening or absence of the vertical lines of the meibomian glands, which may be revealed by transillumination of the everted eyelid using a muscle light or infrared photography.

Tear breakup is a functional measure of tear stability, and in MGD the stability is perturbed,

causing a rapid tear breakup time (TBUT). After a fluorescein strip moistened with sterile saline has been applied to the tarsal conjunctiva, the tear film is evaluated using a broad beam of the slit lamp with a blue filter. This should be done before any manipulation of the eyelids or instillation of other drops (fluorescein-anesthetic combination drops are not suitable for this purpose). The time lapse between the last blink and the appearance of the first randomly distributed dry spot on the cornea is the tear breakup time. The appearance of dry spots in less than 10 seconds is considered abnormal.

Additional clinical findings in MGD include foam in the tear meniscus along the lower eyelid, bulbar and tarsal conjunctival injection, papillary reaction on the inferior tarsus, linear staining along the inferior cornea and inferior conjunctiva, episcleritis, marginal epithelial and subepithelial infiltrates, corneal neovascularization or pannus, and corneal scarring or thinning.

Patients with MGD frequently have acne rosacea. (See the discussion on rosacea later in this chapter.)

Treatment of Dry Eye

Before treatment of dry eye, the eye should be carefully examined for conjunctivochalasis, floppy eyelid syndrome, superior limbic keratoconjunctivitis, and other structural and exogenous disorders that can cause similar symptoms. In addition, the clinician must determine whether the patient has any associated systemic conditions or uses medications that can contribute to dry eye (see the discussion later in this chapter).

ATD and evaporative dry eye frequently coexist. Certain therapeutic interventions, such as artificial tear supplementation, topical cyclosporine, short pulses of topical steroids, and omega-3 fatty acid supplements, are helpful for both conditions. However, certain treatments for ATD can exacerbate evaporative dry eye. For example, punctal occlusion in the presence of active MGD increases the retention of the toxic meibum secretions.

Medical management of aqueous tear deficiency

The selection of treatment modalities for patients with ATD depends largely on the severity of their disease (Table 3-5). Smoking is a risk factor, so advice should be given regarding cessation. It may also be appropriate to modify the patient’s environment in an effort to reduce evaporation of the tear film; a humidifier and/or moisture shields on glasses can be helpful for severe cases.

Table 3-5

Changing or discontinuing any topical or systemic medications that may contribute to the condition should be considered, although it is not always practical. Topical β-blockers have been associated with an increased incidence of dry eye, possibly due to reduced corneal sensitivity. Many systemic medications (diuretics, antihistamines, anticholinergics, and psychotropics) decrease aqueous tear production and increase dry eye symptoms. These drugs should be avoided as much as possible in patients with symptoms of ATD (Table 3-6).

Table 3-6

The mainstay of treatment for ATD is the use of topical tear substitutes (eyedrops, gels, and ointments). Preservative-free tear substitutes are recommended to avoid toxicity in patients who use these agents frequently. Demulcents are polymers added to artificial tear solutions to improve their lubricant properties. Demulcent solutions are mucomimetic agents that can briefly substitute for glycoproteins lost late in the disease process. Demulcents alone, however, cannot restore lost glycoproteins or conjunctival goblet cells, reduce corneal cell desquamation, or decrease osmolarity. Until relatively recently, all demulcent solutions contained preservatives. Preservative-free demulcent solutions were introduced after it was recognized that preservatives increase corneal desquamation. The elimination of preservatives from traditional demulcent solutions has led to improved corneal barrier function, and subsequent attempts have been made to improve function even further by adding various ions to the solutions.

Topical cyclosporine A 0.05% addresses the inflammatory component of ATD and is thus being used earlier in the course of this disease. Therapy is often initiated in combination with a short course of topical steroids, as it may take several months for the anti-inflammatory benefits of cyclosporine to take effect. Approximately 50% of patients with moderate to severe ATD seem to benefit from the use of topical cyclosporine, which to date has shown minimal side effects. Additional agents that prevent T-cell–mediated inflammation are currently being investigated.

Other treatments that have been successfully used to treat severe ATD are dilute solutions of hyaluronic acid and autologous serum drops. The composition of diluted autologous serum is somewhat similar to that of normal tears, particularly in regard to growth factors; therefore, some of the benefit may relate to the trophic function of these substances. Autologous serum drops require blood draws of 3 or 4 red-top tubes. The tubes are spun to separate the serum, then placed on dry ice and sent to a compounding pharmacy, which prepares the solution for the patient. Besides its use in the treatment of ATD, autologous serum may be helpful for persistent epithelial defects and neurotrophic keratopathy.

Treatment of filamentary keratopathy associated with ATD can be challenging. In addition to tear supplementation, acetylcysteine 10%, dispensed in an eyedrop container, can be used as a mucolytic

agent and is helpful in alleviating filaments. Topical low-dose steroids, cyclosporine, or tacrolimus, as well as the use of therapeutic contact lenses, may also be helpful.

In severe cases of ATD, wearing goggles, shields, or moisture bubbles can decrease tear evaporation, although these strategies are generally unacceptable to patients. Therapeutic soft contact lenses may help reduce symptoms in patients with aqueous deficiency but may increase the risk of infection, so patients who use them should be observed more carefully. Scleral contact lenses have been found to be extremely helpful in patients with advanced dry eye symptoms.

Pharmacologic stimulation of tear secretion has been attempted with many compounds, with varying degrees of success. The cholinergic agonists pilocarpine and cevimeline stimulate muscarinic receptors present in salivary and lacrimal glands, thereby increasing secretion. Although studies have shown the 2 agents to be effective in treating both xerostomia and dry eye in patients with Sjögren syndrome, they are approved only for the treatment of xerostomia. It is uncertain whether these agents show long-term benefits, and they are associated with significant adverse effects, which may affect adherence.

Dietary supplementation with omega-3 fatty acids has been shown to increase average tear production and tear volume. Certain fish (eg, salmon, tuna, cod, flounder), shrimp, and crab—as well as flaxseed oil, dark leafy greens, and walnuts—are rich in omega-3 fatty acids. Omega-3 fatty acids block the proinflammatory eicosanoids and cytokines. Commercial preparations of omega-3 fatty acids are also available (eg, TheraTears Nutrition, Advanced Vision Research, Woburn, MA; Dry Eye Omega Benefits, PRN Physician Recommended Nutriceuticals, Plymouth Meeting, PA).

Surgical management of aqueous tear deficiency

Surgical treatment is generally reserved for patients with severe disease for whom medical treatment is either inadequate or impractical. Patients with moderate to severe ATD may be helped by punctal occlusion. Reversible punctal occlusion can be performed in a number of ways, with varying degrees of effectiveness, using collagen implants or silicone punctal plugs (Fig 3-13). Collagen plugs usually dissolve within days and do not provide complete canalicular occlusion. Silicone plugs generally remain in place for months to years unless they fit loosely or are manually displaced. Once a plug has been displaced, subsequent plugs are more likely to be displaced. Most silicone plugs are continuously visible at the slit lamp, making it obvious if they become displaced. One disadvantage of punctal plugs is that they can be inadvertently inserted into the nasolacrimal system and require surgical removal. One type of plug is designed for intracanalicular placement, although it has been associated with infections, requiring surgical removal. If a plug protrudes from the punctum, conjunctival abrasions may occur. Granuloma formation at the punctal opening has been observed and requires removal of the plug. In addition, punctal occlusion may lead to reduced tear flow.

Figure 3-13 Silicone punctal plug. (Courtesy of Robert W. Weisenthal, MD.)

When patients have successfully tolerated reversible punctal occlusion, the most cost-effective manner of performing irreversible punctal occlusion is with a disposable cautery, a hyfrecator, or a radiofrequency probe. Although the procedure is usually permanent, the canaliculi and puncta may recanalize following thermal occlusion. The value of punctal occlusion for ocular surface disease other than dry eye is unproven. The procedure is recommended primarily for patients who have minimal basal tear secretion and punctate keratopathy but not significant ocular surface inflammation or infection; this especially includes older patients, in whom the risk of iatrogenically induced epiphora is minimal. Correction of eyelid malpositions such as entropion and ectropion may also be useful in managing patients with dry eye. Reduction of the palpebral aperture by means of lateral and/or medial tarsorrhaphy can be performed in severe KCS when more conservative measures have failed. However, lateral tarsorrhaphy may limit the temporal visual field and produce a cosmetic defect.

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Kojima T, Higuchi A, Goto E, Matsumoto Y, Dogru M, Tsubota K. Autologous serum eye drops for the treatment of dry eye diseases. Cornea. 2008;27(Suppl 1):S25–S30.

Stevenson W, Chauhan SK, Dana R. Dry eye disease: an immune-mediated ocular surface disorder. Arch Ophthalmol. 2012;130(1):90–100.

Wojtowicz JC, Butovich I, Uchiyama E, Aronowicz J, Agee S, McCulley JP. Pilot, prospective, randomized, double-masked, placebo-controlled clinical trial of an omega-3 supplement for dry eye. Cornea. 2011;30(3):308–314.

Medical management of evaporative dry eye

Management is based on the stage of MGD (Tables 3-7, 3-8). Eyelid hygiene is the mainstay of treatment. Application of warm compresses to the eyelids for at least 4 minutes once or twice a day liquefies thickened meibomian gland secretions and softens adherent incrustations on the eyelid margins. The application of heat should be followed by moderate to firm massage of the eyelids to express retained meibomian secretions. Eyelid massage can be followed by cleansing of the closed eyelid margin with a clean washcloth, a cotton ball, or a commercially available pad. A diluted solution of a nonirritant shampoo, a commercially available solution designed for this purpose, or a dilute sodium chloride solution (1 teaspoon of salt to 1 pint of boiled water) may facilitate cleansing. Performing eyelid hygiene once or twice daily may improve the chronic symptoms of blepharitis.

Table 3-7

Table 3-8

Short-term use of topical antibiotics reduces the bacterial load on the eyelid margin. Therapy with topical ophthalmic azithromycin may be particularly efficacious as it is a lipophilic antibiotic that reduces the production of bacterial lipases and improves the composition of meibomian lipids. The high viscosity of the drop prolongs the contact time and aids its penetration into the glands.

Topical corticosteroids may be required for short periods in cases with moderate to severe inflammation, particularly if there are corneal infiltrates and vascularization. Patients treated with topical corticosteroids should be warned about the potential complications associated with long-term use, because this stubborn condition may lead patients to become dependent.

Patients with blepharitis and obstructive MGD also benefit from changes in diet and omega-3 supplementation. In one study, the use of 1000-mg omega-3 nutritional supplements 3 times a day for 1 year was found to improve symptoms, tear-film stability, and meibomian secretions. In another study, supplementation with fish oil showed no significant effect on meibum lipid composition or