Medication Summary
The goals of pharmacotherapy are to reduce morbidity and to prevent complications. For treatment of dry eye disease (DED), or keratoconjunctivitis sicca (KCS), artificial tears are administered with and without preservatives, depending on severity. Doxycycline 100 mg once daily or twice daily may be given for meibomian gland dysfunction (MGD), if indicated, followed by a supervised decrease in dosage to as low as 20 mg PO QD. Topical cyclosporine 0.05% ophthalmic emulsion is effective FDA-approved treatment for dry eye disease.
Lifitegrast ophthalmic solution is the first prescription specifically approved for dry eye disease by the FDA. It is a lymphocyte function-associated antigen-1 (LFA-1) antagonist.
In addition to the list below, autologous serum eye drops are unpreserved, are nonantigenic by nature, and contain growth factors, fibronectin, immunoglobulins, and vitamins at concentrations similar to or higher than those in natural or artificial tears. Serum eye drops are used for severe dry eye disease with punctate epithelial defects and corneal damage to promote reepithelialization. They can be used successfully in patients who are refractory to other forms of treatment.
Ophthalmic Lubricants
Class Summary
Lubricants act as humectants in the eye. The ideal artificial lubricant should be preservative-free; contain potassium, bicarbonate, and other electrolytes; and have a polymeric system to increase its retention time. Lubricating drops are used to reduce morbidity and to prevent complications. Lubricating ointments prevent complications from dry eyes. Ocular inserts reduce symptoms resulting from moderate to severe dry eye disease.
Artificial tears (Advanced Eye Relief, Bion Tears, Hypo Tears, Murine Tears, Tears Naturale II)
Artificial tears are used to increase lubrication of the eye.
Hydroxypropyl cellulose (Lacrisert)
Hydroxypropyl cellulose acts to stabilize and thicken precorneal tear film and to prolong tear breakup time (TBUT). It is applied as a once- or twice-daily insert into the inferior cul de sac, thereby reducing the ongoing need for continuous application of supplementary topical artificial tears.
Carboxymethylcellulose (GenTeal, Lubricating Plus Eye Drops, Refresh Celluvisc, Refresh Optive, Theratears, Ultra Fresh)
These substances serve as lubricants and emollients.
LFA-1 Antagonists
Class Summary
Intercellular adhesion molecule-1 (ICAM-1) may be overexpressed in corneal and conjunctival tissues in dry eye disease. The integrin lymphocyte function-associated antigen-1 (LFA-1) interacts with ICAM-1 to contribute to the formation of an immunological synapse, resulting in T-cell activation and migration to target tissues. In vitro studies demonstrated that lifitegrast may inhibit T-cell adhesion to ICAM-1 in a human T-cell line and may inhibit secretion of inflammatory cytokines in human peripheral blood mononuclear cells.
Lifitegrast ophthalmic (Xiidra)
Lifitegrast binds to the integrin lymphocyte function-associated antigen-1 (LFA-1), a cell surface protein bound on leukocytes, and blocks the interactions of LFA-1 with its cognate ligand ICAM-1. It is indicated for treatment of the signs and symptoms of dry eye disease in adults.
Mucolytic Agents
Class Summary
Mucolytic agents such as topical 10% N-acetylcysteine lower mucous viscosity by digesting mucoproteins. They are used when mucous discharge or plaques are present.
Acetylcysteine
Mucolytic agents lower mucous viscosity by digesting mucoproteins. They are used when mucous discharge or plaques are present.
Antibiotics, Systemic
Class Summary
Empiric antimicrobial therapy must be comprehensive, covering all likely pathogens in the context of the clinical setting. Oral tetracycline analogues, such as doxycycline and minocycline, have been shown to be effective against meibomian gland dysfunction. They exert the following 4 types of effects:
- Antibacterial effects, resulting from a reduction in the bacterial load on the eyelid; despite considerable antimicrobial resistance in common ocular surface flora and pathogens, long-term tetracycline analogue therapy has not been shown to promote infectious complications by resistant organisms
- Antiangiogenic effects
- Anti-inflammatory effects, resulting from a decrease in activity of collagenase, phospholipase A2, and several matrix metalloproteinases (MMPs), as well as from a decrease in the production of interleukin (IL)-1 and tumor necrosis factor alpha (TNF-α)
- Inhibition of lipase production, which decreases production of diglycerides and free fatty acid (FFA) in meibomian secretions (FFA can destabilize the tear film and can cause inflammation)
- Doxycycline and minocycline are preferred over tetracycline because they are more lipophilic and achieve a higher target tissue concentration, while having a more tolerable systemic side effect profile.
- Azithromycin is an additional antibacterial agent with anti-inflammatory effects that may be beneficial for treating dry eye disease. This drug, in low doses, inhibits the NFκB pathway with a resultant decrease in MMP activity and decreased levels of IL-8, RANTES, IL-1β, and TNF-α. However, it should be used with caution, as macrolide antibiotics may have notable systemic side effects.
Doxycycline (Acticlate, Adoxa, Doryx, Doxy 100, Solodyn, Targadox, Vibramycin)
Doxycycline inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Minocycline (Minocin, Solodyn)
Minocycline treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma.
Immunosuppressants
Class Summary
Systemic immunosuppressants are indicated when dry eye disease is accompanied by a CTD with significant systemic complications.
Cyclosporine ophthalmic (Restasis, Cequa, Vevye)
Cyclosporine may act as a partial immunomodulator. The exact mechanism of action is not known, although it inhibits T-cell function and inhibits calcineurin. Cyclosporine emulsion has never been shown to place patients at risk of any ocular or systemic infections.
Corticosteroids
Class Summary
Corticosteroids have anti-inflammatory properties with diverse mechanisms of action and cause profound and varied metabolic effects. They modify immune response to diverse stimuli. Inflammation is the key component of the pathogenesis of dry eye disease. Topical corticosteroids can be used to reduce the inflammation.
Loteprednol etabonate (Lotemax, Alrex, Inveltys, Eysuvis)
Loteprednol etabonate decreases inflammation by numerous mechanisms, including suppressing migration of polymorphonuclear leukocytes (PMNs), reducing production of inflammatory mediators at the nuclear mRNA level, and reversing increased capillary permeability. It is a topical ester steroid available in 0.2%, 0.25%, 0.5%, and 1% drops that is associated with a decreased risk of glaucoma and cataractogenesis.
Fluorometholone (Flarex, FML, FML Forte)
Fluorometholone inhibits edema, fibrin deposition, capillary dilation, phagocytic migration, capillary proliferation, collagen deposition, and scar formation. It decreases inflammation and corneal neovascularization, suppresses migration of PMNs, and reverses capillary permeability. It is believed to act by inducing phospholipase A2 inhibitory proteins. Used topically, fluorometholone can elevate intraocular pressure (though more slowly than dexamethasone phosphate does) and cause steroid-response glaucoma.
Nutritionals, Other
Class Summary
Certain dietary supplements may have beneficial effects.
Omega-3 fatty acids (Lovaza)
Omega-3 fatty acids may have anti-inflammatory effects and may inhibit leukocyte function. Numerous preparations are available for point-of-service sales and provide pharmaceutical-grade, mercury-free sources of essential fatty acids known to improve ocular surface function.
Cholinergic Agonists
Class Summary
Cholinergic agonist activity activates the trigeminal parasympathetic pathway resulting in increased production of basal tear film.
Varenicline intranasal (Tyrvaya)
Varenicline nasal spray is a water-soluble agonist for nicotinic cholinergic receptor. It increases lacrimal unit production of tear film by stimulating trigeminal nerve within the nasal cavity. It is currently approved for the treatment of signs and symptoms of DED.
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Eye tear system anatomy: a. tear gland / lacrimal gland, b. superior lacrimal punctum, c. superior lacrimal canal, d. tear sac / lacrimal sac, e. inferior lacrimal punctum, f. inferior lacrimal canal, g. nasolacrimal canal.
Tables
Variable |
Dry Eye Severity Level |
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1 |
2 |
3 |
4 (must have signs and symptoms) |
|
Discomfort (severity and frequency) |
Mild, episodic; occurs under environmental stress |
Moderate, episodic or chronic; occurs with or without stress |
Severe, frequent, or constant; occurs without stress |
Severe or disabling, constant |
Visual symptoms |
None or episodic mild fatigue |
Annoying or activity-limiting, episodic |
Annoying, chronic, or constant; activity-limiting |
Constant and possibly disabling |
Conjunctival injection |
None to mild |
None to mild |
+/– |
+/++ |
Conjunctival staining |
None to mild |
Variable |
Moderate to marked |
Marked |
Corneal staining (severity and location) |
None to mild |
Variable |
Marked central |
Severe punctate erosions |
Corneal and tear signs |
None to mild |
Mild debris, decreased meniscus |
Filamentary keratitis, mucus clumping, increased tear debris |
Filamentary keratitis, mucus clumping, increased tear debris, ulceration |
Lid and meibomian glands |
MGD variably present |
MGD variably present |
MGD frequent |
Trichiasis, keratinization, symblepharon |
Tear breakup time |
Variable |
≤ 10 s |
≤ 5 s |
Immediate |
Schirmer score |
Variable |
≤ 10 mm/5 min |
≤ 5 mm/5 min |
≤ 2 mm/5 min |
MGD=meibomian gland dysfunction. |
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