D ry eye is a multi-factoral disease of the tears and ocular surface; one such factor is the patient’s use of systemic medications.¹ Many common systemic medications can affect ocular tissues, and medications that contribute to dry eye symptoms are present in many categories of commonly prescribed and over-the-counter (OTC) medications. According to one estimate, four out of every five U.S. adults will use prescription medicines, over-the-counter drugs or dietary supplements in any given week, and nearly one-third of adults will take five or more different medications in the same timeframe.² Older patients may be at greater risk for medication side effects because they often take multiple prescription medications. Of our patients who take six or more medications a week, at least half receive prescriptions from three or more physicians!³

In this article we will discuss several categories of pharmaceuticals, each containing medications that can produce dry eye symptoms. Pharmaceuticals that can cause dry eye symptoms include certain medications used to treat hypertension such as central-acting agents and diuretics; antihistamines and decongestants, in concert with anticholinergics; hormones; certain antidepressants; pain relievers, such as ibuprofen and lortab; and dermatologic agents.

Hypertensive Agents
Physicians prescribe systemic beta blockers to treat angina pectoris, essential hypertension, myocardial infarctions and migraine headaches.⁴ Beta blockers reduce lysozyme levels and immunoglobulin A, causing a decrease in aqueous production and subsequently leading to symptoms of dry eye.⁵ Patients using beta blockers also exhibit corneal anesthesia, decreased tear film break-up times and ocular irritation.

Thiazides or diuretics are often prescribed to treat congestive heart failure. This drug class causes decreased lacrimation, which may induce dry eye complaints. Hydrochlorothiazide (HCTZ) is a commonly used diuretic and can produce changes in the precorneal tear film, inducing a dry eye.⁶ Furosamide and HCTZ/triamterene are other common medications in this class.

Lissamine green staining of conjunctiva and cornea in dry eye.

Antihistamines and Decongestants
Medications that block histamine receptors alleviate allergic conditions of rhinitis, uticaria, dermatitis and systemic allergies. The drugs in this class reduce mucous and aqueous production, which cause dry eye complaints.⁷ Their activity may also decrease the aqueous component of the precorneal tear film. In general, these effects occur with OTC preparations—most commonly with Benadryl (diphenhydramine, McNeil Consumer) and Chlor-Trimeton (chlorpheniramine, Schering)—and in recent offerings, such as Claritin (loratadine, Schering).

The newer, more site-specific (H1 selective) antihistamines like Zyrtec (cetirizine, McNeil Consumer), Clarinex (desloratadine, Merck) and Allegra (fexofenadine, Sanofi-Adventis) are less likely to cause ocular dryness, but they may affect the tear film. The effect of these medications, however, is not as profound as earlier generation antihistamines.

Antihistamines are combined with anticholinergics in many OTC medications, such as cold preparations, sedatives, antidiarrheals and nasal decongestants.⁸ These combination medications induce dry eye, along with the commonly known effects of anticholinergics, which include mydriasis and decreased papillary response to bright light.⁸

Hormones
Hormone replacement therapy (HRT) with estrogens alone or in combination with progestins is a commonly prescribed therapy for post-menopausal women. The use of estrogen replacements and contraceptive agents is commonly implicated in dry eye. The exact cause-and-effect relationship is unknown, but may be associated with a decreased aqueous component of the precorneal tear film.⁹

A great deal of information is available about hormone replacement therapy in post-menopausal women. Debra A. Schaumberg, Sc.D., O.D., M.P.H., and colleagues reported a 69% increase in dry eye symptoms in women who were taking estrogen compared to the control group.¹⁰ Additionally, the study reported that women who were taking a progesterone or progesterone combination also experienced a 29% increase in dry eye symptoms over women not on HRT.

This report, based on observations on 25,000 post-menopausal women, showed evidence of a significant increased risk of dry eye syndrome and severity of dry eye symptoms in women taking estrogen. Because this risk has been shown to increase with longer durations of estrogen use, patients on HRT with estrogens should be monitored for dry eye problems.¹¹

Antidepressants
Widely prescribed anti-anxiety medications and tricyclic antidepressants can produce dry eye side effects. Symptoms of blurred vision, cycloplegia and dry eye are transient and reversible.⁷

Two well-known antidepressants are Zoloft (sertraline, Pfizer) and Paxil (paroxetine, GlaxoSmithKline). Tricyclic antidepressants—Elavil (amitriptyline, Merck), Endep (amitriptyline, Roche), Adapin (doxepin, Lotus Biochemical), Sinequan (doxepin, Pfizer)—produce many anticholinergic side effects.¹² These medications are being prescribed to a broader and younger population than in the past, which means there is an increased likelihood that your patients will display dry eye side effects.

Pain Relievers
Ibuprofen, a common OTC pain medication, can cause dry eye in addition to blurred vision, refractive changes, diplopia and color vision changes, especially when the higher dosages (up to 800mg) are prescribed.¹³ Darvocet-N (propoxyphene napsylate and acetometaphin, USP) reportedly decreases tear secretion.¹⁴ Lortab (hydrocodone and acetaminophen, USP) combinations can also produce a dry eye.

Dermatologic Medications
Dermatologists sometimes prescribe Accutane (isoretinoin, Genpharm) for the treatment of recalcitrant acne. Even though Roche Pharmaceuticals pulled Accutane from the market in 2009, generic versions of the drug may still be available by prescription.

Isotretinoin (13-cis-retinoic acid) is a form of vitamin A that reduces the amount of oil released by oil glands in the skin.¹⁵ Vitamin A and its synthetic derivatives are collectively known as retinoids and are used to treat severe recalcitrant nodular acne, acne vulgaris and severe recalcitrant psoriasis, and to induce remission of leukemia.¹⁶ Isoretinoin has been shown to be secreted in tears by the lacrimal gland and has been associated with causing meibomian gland dysfunction—producing dry eye complaints, contact lens discomfort, blepharoconjunctivitis, transient blurring of vision and acute, transient refractive changes––especially myopic shifts.¹⁷ This synthetic medication affects the overproduction of skin lipids. Decreased meibomian gland function also impacts the production of the lipid layer of the precorneal tear film, leading to tear film instability and enhanced surface evaporation, which results in dry eye syndrome.

Dry eye complaints will disappear after medication use is discontinued, although it may take several months for the complaints to wane. Approximately 20% of previously successful contact lens wearers may need to decrease their wearing time, use preservative-free lubricating eye drops or discontinue contact lens wear while on this medication.¹⁸

Gastrointestinal Medications
This medication class includes the proton pump inhibitors: Prevacid (lansoprazole, Takeda), Prilosec (omeprazole, Procter & Gamble), Nexium (esomeprazole magnesium, AstraZeneca), Zantac (ranitidine, GlaxoSmithKline) and Tagamet (cimetidine, GlaxoSmithKline). Proton pump inhibitors have caused dry eye complaints, although this information does not appear in their individual package inserts. H2 receptor antagonists, like all antihistamines, can cause dry eye symptoms.

Chemotherapy Medications
A major drug in this class is Cytoxan (cyclophosphamide, Bristol-Myers Squibb), which is also used to treat ocular cicatricial pemphigoid and primary Sjögren syndrome. As many as 60% of patients taking cyclophosphamide have developed dry eye.¹⁹

Antipsychotic Medications
Phenothiazines are prescribed to manage schizophrenia. Mellaril (thioridazine, Mutual Pharmaceutical) is the best known of this class and has almost completely replaced Thorazine (chlorpromazine, GlaxoSmithKline) in the management of the condition. Both drugs decrease aqueous secretion, and symptoms are transient and dose dependent.²⁰

Do not consider this brief discussion exhaustive, as many other drugs and categories may have dry eye as a side effect. While these drug categories are the most common offenders in producing dry eye problems, exceptions exist in every drug category. No one can possibly remember all of the potential ocular adverse events associated with each medication. Fortunately, there are many resources available to help us with this information.

Two useful resources in clinical practice are “Clinical Ocular Toxicology: Drug Induced Ocular Side Effects” by Frederick Fraunfelder, M.D., and Wiley Chambers and “Clinical Ocular Pharmacology,” 5th edition by James Bartlett, O.D., D.O.S., M.Sc., and Siret Jaanus, Ph.D., L.H.D.
When selecting reference resources, choose those that are complete and updated frequently. Perhaps none is more current and readily available than Epocrates (www.epocrates.com), which is updated weekly can be downloaded to your mobile device.

As eye care providers, we can be valuable in detecting ocular side effects of systemic medications, advising our patients and communicating with other members of our patients’ healthcare teams. As always, the best course is to educate our patients about the role their medications play in their dry eye complaints.

Patients need to assume some responsibility here as well. They need to know the brand names and generic names of the medications they are taking. Recommend your patients use only one pharmacy so the pharmacist can help monitor for drug interactions. At the end of the day, it is our responsibility to make sure that our patients know how their systemic medications could be contributing to their ocular surface disease. 

Dr. Bowling is in private group practice in Tuscaloosa, Ala. He is also a diplomate in the Primary Care Section of the American Academy of Optometry.

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