Treatment of Dry Eye
Before treatment of dry eye is initiated, the eye should be carefully examined for conjunctivochalasis, floppy eyelid syndrome, superior limbic keratoconjunctivitis, nighttime lagophthalmos, and other structural and exogenous disorders that can cause symptoms similar to those of dry eye. In addition, the clinician must determine whether the patient has any associated systemic conditions (eg, Parkinson disease or mucous membrane pemphigoid) or uses medications that can contribute to dry eye, such as drugs with antihistaminic or anticholinergic properties (see “Medical management of aqueous tear deficiency”).
ATD and evaporative dry eye frequently coexist. Certain therapeutic interventions, such as artificial tear supplements, topical cyclosporine, short pulses of topical corticosteroids, 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
Selection of the treatment modalities for patients with ATD depends largely on the severity of their disease (Table 3-7). Since smoking is a risk factor for dry eye, 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 in severe cases.
Changing or discontinuing any topical or systemic medications that may contribute to the condition should be considered, although this is not always practical. Topical β-blockers have been associated with an increased incidence of dry eye, and many systemic medications (diuretics, antihistamines, and anticholinergic and psychotropic drugs) 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 3-8).
Table 3-7 Therapeutic Options for Aqueous Tear Deficiency
The mainstay of treatment for ATD is the use of tear substitutes (drops, gels, and ointments). Preservative-free tear substitutes are recommended to avoid the toxic effects that can arise with dosing more than 4 times daily. 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 tear film 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 in patients using these agents, and subsequent attempts have been made to improve function even further by adding various ions to the solutions. Liposomal sprays, applied to the closed eyelids by a sterile spray mechanism, may help support the tear film. Hydroxypropyl cellulose inserts are occasionally helpful for patients unable to frequently instill artificial tears.
Table 3-8 Medications With Anticholinergic Side Effects That Decrease Tear Production
Topical cyclosporine A 0.05% addresses the inflammatory component of moderate to severe ATD and is thus being used earlier in the disease course. Therapy is often initiated in combination with a short course of topical corticosteroids to provide an initial reduction in surface inflammation. Patients should be advised that it may take many months of consistent twice-daily use before they obtain symptomatic relief, which results from the anti-inflammatory benefits of cyclosporine.
Lifitegrast 5% eyedrops, used twice daily from unit-dose vials, was approved by the US Food and Drug Administration (FDA) in 2016 to treat the symptoms and signs of dry eye disease. Lifitegrast may inhibit the migration and activation of T-cells and the subsequent release of inflammatory cytokines by blocking the interaction of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1. Patients generally know within a few weeks whether this treatment will be beneficial. Lifitegrast can cause mild irritation, transient blurred vision, and altered taste perception. Contact lenses should not be inserted for at least 15 minutes after eyedrop instillation.
Other treatments that have been successful in patients with severe ATD are dilute solutions of hyaluronic acid and autologous serum drops. Autologous serum drops require blood draws of 3 or 4 red-top tubes. The tubes are spun to separate the serum; they are 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 patients with persistent epithelial defects and neurotrophic keratopathy.
Treatment of filamentary keratopathy associated with severe ATD can be challenging. Filaments should be debrided with a jeweler’s forceps or a cotton swab soaked with topical anesthetic. Treatment directed at enhancing the tear film reduces the severity of recurrence. In addition to tear supplementation and punctal occlusion, acetylcysteine 10%, dispensed with an eyedrop container, can serve as a mucolytic agent and may further reduce filament formation. Topical low-dose corticosteroids, cyclosporine, and therapeutic soft contact lenses may be helpful. While therapeutic soft contact lenses may be beneficial for treatment of filamentary keratitis due to other causes, bandage soft contact lenses are rarely used to reduce symptoms in patients with ATD, because they may be associated with an increased risk of infection. Patients who use them should therefore be observed carefully. Scleral contact lenses have been found to be extremely helpful in patients with advanced dry eye symptoms.
In severe cases of ATD, use of moisture-retaining eyewear, also called moisture chamber glasses (glasses, goggles, or sunglasses incorporating a moisture shield or seal), can decrease tear evaporation; however, all but the most severely affected patients may find this therapy cosmetically objectionable.
Pharmacologic stimulation of tear secretion has been attempted using many compounds, with varying degrees of success. The cholinergic agonists pilocarpine and cevimeline hydrochloride 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 by the FDA only for the treatment of xerostomia. It is uncertain whether these agents provide long-term benefits, and they are associated with significant adverse effects, which may affect patient 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) and crustaceans (shrimp and crab), flaxseed oil, dark leafy greens, and walnuts are rich in omega-3 fatty acids, which block proinflammatory eicosanoids and cytokines. Commercial preparations of omega-3 fatty acids are also available and include TheraTears Eye Nutrition (Akorn Consumer Health, Lake Forest, IL), Dry Eye Omega Benefits (PRN Physician Recommended Nutriceuticals, Plymouth Meeting, PA), HydroEye (ScienceBased Health, Houston, TX), and Systane Vitamin (Alcon, Fort Worth, TX).
Epitropoulos AT, Donnenfeld ED, Shah ZA, et al. Effect of oral re-esterified omega-3 nutritional supplementation on dry eyes. Cornea. 2016;35(9):1185–1191.
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.
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.
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 benefit from punctal occlusion, which can be temporary, semipermanent, or permanent. Reversible punctal occlusion can be performed using collagen implants or silicone punctal plugs and has varying degrees of effectiveness (Fig 3-13). Collagen plugs usually dissolve within days and do not provide complete canalicular occlusion. Intracanalicular plugs made of polydioxanone (eg, VisiPlug; Lacrimedics Inc, Eastsound, WA) provide occlusion for up to 6 months. These plugs can be seen by transilluminating the eyelid, enabling the clinician to determine whether they have become displaced or eroded. The Extend plug, another absorbable implant (Beaver-Visitec International, Waltham, MA), dissolves over a 3-month period. Permanent intracanalicular plugs have been associated with infectious canaliculitis and sterile inflammation, which in some cases have required canaliculotomy and dacryocystorhinostomy. The absorbable intracanalicular plugs may be less likely to cause such problems; however, clinicians should be aware of the risk of intracanalicular inflammation.
Silicone plugs may remain in place for months or years unless they are inadequately sized or are manually displaced. For example, Parasol plugs (Beaver-Visitec International) have a high retention rate. Some plugs have a small hole bored through the center to reduce the likelihood of epiphora. Most silicone plugs are continuously visible at the slit lamp, making it obvious if they become displaced or eroded.
Figure 3-13 Silicone punctal plug.
(Courtesy of Robert W. Weisenthal, MD.)
If inserted too forcefully, punctal plugs can be inadvertently inserted into the canaliculus and may require surgical removal. If a plug protrudes from the punctum, conjunctival irritation or abrasion may occur. Granuloma formation at the punctal opening has been seen and may require removal of the plug and possible excision.
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 subsequently recanalize.
The value of punctal occlusion for ocular surface disease other than tear deficiency is unproven. The procedure is recommended primarily for patients who have minimal basal tear secretion and punctate keratopathy but no significant ocular surface inflammation or infection. Correction of eyelid malpositions such as entropion and ectropion may also be beneficial in managing patients with dry eye symptoms. 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 an undesirable cosmetic deformity.
American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern Guidelines. Dry Eye Syndrome. San Francisco: American Academy of Ophthalmology; 2013. Available at www.aao.org/ppp.
The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop. Ocul Surf. 2007;5(2):75–92.
Marcet MM, Shtein RM, Bradley EA. Safety and efficacy of lacrimal drainage system plugs for dry eye syndrome: a report by the American Academy of Ophthalmology. Ophthalmology. 2015;122(8):1681–1687.
Mazow ML, McCall T, Prager TC. Lodged intracanalicular plugs as a cause of lacrimal obstruction. Ophthal Plast Reconstr Surg. 2007;23(2):138–142.
Stevenson W, Chauhan SK, Dana R. Dry eye disease: an immune-mediated ocular surface disorder. Arch Ophthalmol. 2012;130(1):90–100.
Medical management of evaporative dry eye
Management is based on the stage of MGD; see Tables 3-9 and 3-10. Eyelid hygiene is the mainstay of treatment. Application of warm compresses to the eyelids twice daily for 3–5 minutes liquefies thickened meibomian gland secretions and softens adherent crusts on the eyelid margins. The patient should be warned to avoid excessive or uneven heat if a microwave is used for the compress. 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 wash-cloth or a commercially available pad. A solution prepared with a nonirritating shampoo and water or a commercially available solution designed for this purpose may facilitate cleansing.
Table 3-9 Clinical Summary of the MGD Staging Used to Guide Treatment
Table 3-10 Treatment Algorithm for Meibomian Gland Dysfunction
Short-term or periodic use of topical antibiotics reduces the bacterial load on the eyelid margin. Topical azithromycin ophthalmic solution 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. Long-term use of topical antibiotics or subtherapeutic dosing can result in the development of resistant organisms.
Topical corticosteroids may be required for short periods in cases with moderate to severe inflammation, particularly if corneal infiltrates and vascularization are present. Patients treated with topical corticosteroids should be warned about the potential complications associated with long-term use.
Patients with blepharitis and obstructive MGD benefit from dietary changes 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 aqueous tear evaporation rate, but average tear production and tear volume increased. Therefore, the mechanism of action of omega-3 supplementation for MGD is not yet established.
Treatment with oral tetracyclines can be very effective; however, patients with MGD should be informed that therapy may only control their condition, not eliminate it. Because tetracycline must be taken on an empty stomach and requires more frequent dosing, doxycycline and minocycline are increasingly used. The dosages for doxycycline and minocycline are 100 mg and 50 mg, respectively, every 12 hours for 1–2 weeks; the dose for each drug is tapered to 50 mg daily. Even lower doses may be equally effective. Therapy must often be repeated to achieve long-term control. If long-term therapy is required, a 1-week structured treatment interruption each month may reduce the risk of yeast infection. Erythromycin can be used as alternative therapy in children or in patients with known hypersensitivity to tetracycline.
Adverse effects of oral tetracyclines include photosensitization, gastrointestinal upset, and, in rare instances, azotemia. Long-term use may lead to oral or vaginal candidiasis in susceptible patients. The use of tetracyclines is contraindicated during pregnancy, in women who are breastfeeding, and in patients with a known hypersensitivity to these agents. These agents should be used with caution in women of childbearing age, women with a family history of breast cancer, and patients with a history of liver disease. Oral tetracyclines can also potentiate the effect of certain anticoagulants (eg, warfarin). In addition, these antibiotics should be avoided in children younger than 8 years because they cause permanent discoloration of teeth and bones in this population. Tetracyclines may reduce the efficacy of oral contraceptives. Oral azithromycin is an alternative treatment, but it may be hazardous when used in patients with cardiovascular problems. In March 2013, the FDA issued a warning that oral azithromycin may lead to abnormalities in the electrical activity of the heart, with the potential to create serious irregularities in heart rhythm.
Recently, several new modalities have been introduced for the treatment of MGD. Mechanical meibomian gland probing using special instruments (Maskin Meibomian Gland Intraductal Probe; Rhein Medical Inc, St Petersburg, FL) lyses a fibrovascular membrane growing into the duct and may facilitate gland function, permitting normal secretion of meibum. The LipiFlow thermal pulsation system (TearScience, Morrisville, NC), which combines gentle pulsatile pressure and thermal energy to increase blood flow to the eyelid and open obstructed meibomian gland ductules, may be an appropriate alternative when conventional treatment has failed to improve symptoms. Variable improvement in dry eye symptoms has been achieved with this treatment modality; however, it is expensive and may need to be repeated. Adverse effects of LipiFlow, which are self-limited, include conjunctival hyperemia, edema, hemorrhage, and surface staining. The safety and efficacy of LipiFlow have not been established in moderate to severe allergic or vernal conjunctivitis, in the presence of severe eyelid inflammation, or for dry eye related to systemic disease. LipiFlow should not be used in the presence of active infection, postoperatively, or in the presence of functional abnormalities of the eyelid. The MiBoFlo Thermoflo (Mibo Medical Group, Dallas, TX) utilizes a thermoelectric heat pump to promote liquefaction of meibum; the device is applied to the eyelid skin manually, supplying continuous heat. Intense pulsed-light (IPL) therapy (Lumenis, San Jose, CA), a concentrated heat treatment, may also be used to treat MGD. The efficacy of these treatments has not been proven in well-designed, prospective, randomized, controlled studies.
American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern Guidelines. Blepharitis. San Francisco: American Academy of Ophthalmology; 2013. Available at www.aao.org/ppp.
Foulks GN, Lemp MA. Meibomian gland dysfunction and seborrhea. In: Mannis MJ, Holland EJ, eds. Cornea. Vol 1. 4th ed. Philadelphia: Elsevier; 2017:357–365.
Macsai MS. The role of omega-3 dietary supplementation in blepharitis and meibomian gland dysfunction. Trans Am Ophthalmol Soc. 2008;106:336–356.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.