Pharmacological Treatment

Pharmacological options

Pharmacological options for the treatment of dry eye syndrome (DES) include both topical agents (typically the preferred form of pharmacologic treatment) and oral systemic drugs. Drugs used in topical therapy include anti-inflammatory agents such as cyclosporine A, lifitegrast, azithromycin and glucocorticoids, and perfluorohexyloctane – a recently approved tear film stabilizer. Topical secretagogues (i.e., inducers of aqueous tear and mucin production) may be effective but are not usually used in the United States. Systemic drugs include oral azithromycin and oral doxycycline. Another option is varenicline, which promotes tear production via chemical nasolacrimal reflex (NLR) stimulation. The oral secretagogues pilocarpine and cevimeline are discussed in the Treatment for Severe Disease subsection.

Cyclosporine, a non-steroidal anti-inflammatory and immunomodulatory antimetabolite derived from fungi and most commonly used in patients with autoimmune diseases and organ transplants, can be formulated in a low concentration solution (0.05-2%) for ophthalmic use. Its efficacy for amelioration of DES symptoms is well supported evidentially.

Lifitegrast is a T-cell integrin antagonist that blocks the binding of lymphocyte function-associated antigen 1 (LFA-1) to intracellular adhesion molecule 1 (ICAM-1) and thus inhibits lymphocyte infiltration of the ocular surface. It is formulated as a 5% solution for ophthalmic use. It has documented efficacy in reducing signs and symptoms of DES, including both tear film breakup time (TBUT) and Ocular Surface Disease Index (OSDI) scores.

Azithromycin, a macrolide antibiotic, is particularly useful for the treatment of evaporative dry eye (EDE). It can be administered either in topical form (as a 1.0% or 1.5% solution) or orally (500 mg per day). Its efficacy in improving the signs and symptoms of Meibomian Gland Dysfunction (MGD)-associated DES is believed to derive in large part from its unique stimulatory effects on meibomian gland epithelial cell function (which are not shared by other macrolides) rather than any anti-microbial activity.

Glucocorticoids are powerful anti-inflammatory agents, and have established efficacy for the treatment of DES. Topical formulations include prednisolone 1%, loteprednol 0.5% and fluorometholone 0.1% or 0.25% suspension. Because of potential adverse effects (glaucoma, cataract formation) associated with prolonged (>4 week) glucocorticoid use, the risks and benefits should be carefully weighed before they are prescribed.

Perfluorohexyloctane is a novel (approved in 2023) semifluorinated alkane which stabilizes the tear film by forming a monolayer at its surface, although its exact mechanism of action is currently unknown. It has good efficacy and is available as a prescription-only, preservative-free ophthalmic solution appropriate for patients with moderate EDE.

Doxycycline is a tetracycline antibiotic that, in addition to its anti-inflammatory properties, is also thought to reduce the levels of bacterial lipolytic exoenzymes (secondary to its anti-microbial properties), which in turn reduces the levels of meibomian lipid breakdown products, improving meibomian gland function. Like azithromycin, it can be useful for the treatment of MGD-associated DES, and is typically taken orally (at a dose of 40-200 mg per day).

Varenicline is a nicotinic acetylcholine receptor (nAChR) agonist that increases tear production by chemically stimulating the nasolacrimal reflex (NLR), although the exact molecular details of its mechanism of action are currently unknown. It is delivered via a nasal spray, and demonstrated efficacy in improving signs and symptoms of DES over a period of at least 12 months in three pivotal clinical trials.

A summary of the pharmacological treatment options discussed above is presented in Table 3-2.

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