The Dry Eye Zone

Rebecca's Blog

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Drying Drugs

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A few fascinating facts

  • Drugs can cause dry eye up to five different ways. 
  • 22 of the 100 best-selling drugs in the US are believed to possibly cause dry eye.
  • There are 9 drugs which are known to secrete into the tear film, and of these, 8 are associated with causing dry eye.
  • The elderly are the most at risk. 

SOURCE: TFOS DEWS II Iatrogenic dry eye report, section 4

Who suffers from drug-induced dry eye?

With the emergence of medically induced dry eye, including drug induced dry eye, the demographics of dry eye changed dramatically, even without all the lifestyle factors contributing to dry eye. Anyone, regardless of gender or age, can have heightened risk from the drying effects of systemic drugs. 

This is why those of us who have dry eye, and know what it's like and how much it can impact our lives, need to be part of the process of educating people around us. I don't mean that everybody needs to worry about dry eye, but that they need to know how it shows up, and what to do if it does.

1. The elderly.

In a widely cited population study, it was found that 62% of dry eye disease cases in the elderly were attributable to systemic drugs. 12 different classes of drugs were cited.

Am I going out of my way to draw attention to this? You bet. How many of us have elderly parents, grandparents or other family members or loved ones? When they complain about their eyes, please take them seriously. The amount of discomfort that dry eye can cause is hugely underestimated and misunderstood. The elderly are the most likely to have ongoing medication risk factors that they cannot avoid - but they also have a constellation of other risk factors teaming up with the meds, like cataract surgery, or glaucoma drops, on top of the natural effects of aging on the tear system.

Our aging loved ones need to be able to see comfortably to sustain quality of life. Ensuring that they have suitable diagnosis and treatment of dry eye, and providing them with the tools to keep their eyes comfortable, should be priorities for caregivers and loved ones.

2. Kids.

With acne.

Because retinoic acid, a/k/a Accutane, can cause dry eye and blepharitis - but it can even induce atrophy of the meibomian glands and cause changes in tear film stability, lipids and osmolality.

We've had many young people in our forums over the years whose meibomian glands were badly damaged by relatively short courses of this drug.

3. People who get botox injections.

Botox can cause you to temporarily not be able to close your eyes, causing dryness.

4. People with allergies.

No surprise - antihistamines are drying.

5. Women on HRT.

In the famous Beaver Dam study, systemic hormones were associated with a 71% increase in the likelihood of dry eye symptoms in women under the age of 50. HRT dry eye risk was underscored by the Women's Health Study of 25,000 postmenopausal women as well as the Extension Blue Mountains Eye Study of 1174 participants aged 50 or over.

6. People suffering from depression or anxiety.

The Veterans Affairs Administration database of over 2 million patients showed anti-depressant and anti-anxiety medications were associated with increased risk of dry eye. This is true of anti-cholinergics as a class (did you know that anti-depressants and anti-psychotics are anti-cholinergics?)

7. Or high blood pressure.

All about beta blockers.

8. Or cancer.

Chemotherapy can cause changes to both tear secretion and tear film quality.

9. And anybody taking 5 or more systemic drugs.

These are just examples.

Because anyone taking certain classes of drugs can be at higher risk of dry eye, especially if they have other risk factors as well.

SOURCE: TFOS DEWS II Iatrogenic dry eye report, section 4

    What can we do to prevent it?

    Some people have the gift of health and the determination to avoid systemic drugs, and can avoid them altogether. That's great.

    But there are a lot of drugs that may be necessary to maintaining health - or life itself - for people with certain diseases. There are many others that may be key to maintaining quality of life. So here's how I think about navigating drying drugs.

    1. Ditch the dogmatic, simplistic approach, and think "big picture".

    It's not practical to just avoid all drying drugs on principle. Unless, of course, you don't actually need any! 

    Few things annoy me more, for example, than hearing of doctors who simply tell all dry eye patients not to take antidepressants because they will dry their eyes out more. I don't know any ophthalmologists who are also board certified in psychiatry, and in my opinion, they have no business making the risk/reward assessment for someone using or considering antidepressants. Advising people of risks, and recommending that they talk to their mental health provider about alternatives - those are great. But scaremongering and discouraging someone who may be suffering from very serious depression is a disservice.

    2. TFOS DEWS II recommendations

    TFOS DEWS II suggests the following possibilities, so if you are concerned about a drug you are on and whether it may be causing dry eye, here are some things to talk with your doctor about:

    • Testing (stopping and restarting) to be sure the drug is really the culprit. 
    • Switching to an alternative 
    • Reducing dosage
    • Compensating with more lubricants or other dry eye treatments
    • And... making better drugs that don't have this side effect!

    3. Explore alternatives, and ask your doctor to help.

    This is where it gets really interesting!

    If you have dry eye, and are concerned about the drying effects of a drug you are taking or may have to consider, it can be a great inducement to put in more research on the drug and its alternatives than you might have otherwise. 

    One of the interesting findings I noted from the TFOS DEWS II Iatrogenic Dry Eye report (the bible on medically induced dry eye) was that although there are so many studies about this, the vast majority are about classes of drugs, not individual drugs. Consider:

    Most of the studies available on systemic drug-induced DED analyze only the classes of drugs, but not individual prescription drugs. Overall, systemic drugs may cause dry eye secondary to decreased tear production, altered nerve input and reflex secretion, inflammatory effects on secretory glands, or direct irritation effects through secretion into the tears. However, not every drug does actually reach the ocular surface structures. Rather certain drug properties and kinetics play a role in determining which drugs penetrate intraocularly, namely, lipid solubility, molecular weight, ionic state, plasma protein binding and total blood concentration. TFOS DEWS II Iatrogenic Dry Eye Section 4.1.1

    In many cases, there really are alternatives that may have a different dry eye profile.

    4. Remember that "can" does not mean "will".

    Just because a drug can cause or worsen dry eye does not mean it will do so for everyone under all circumstances. It's a matter of heightened risk.

    Which drugs cause or contribute to dry eye?

    TFOS DEWS II Iatrogenic Dry Eye Report lists them in two different tables - one that summarizes big epidemiological studies that draw correlations and suggest what drugs may put people at higher risk for dry eye, and one that identifies drugs or drug classes that were specifically studied and which were concluded to "cause, contribute to or aggravate" dry eye. 

    "Elevated dry eye risk" drug classes

    Source: Table 2, TFOS DEWS II Iatrogenic Dry Eye Report

    • NSAIDS
    • Diuretics
    • Vasodilators
    • Analgesics/antipyretics
    • Antiulcer agents
    • Sulfonylureas
    • Cardiac glycosides
    • Anxiolytics/benzodiazepines
    • Anti-infectives
    • Antidepressants/antipsychotics
    • Antihypertensives
    • Antihistamines
    • Inhaled steroid use
    • Systemic corticosteroids
    • Systemic hormones in women <50yr
    • Hormone replacement therapy in postmenopausal women
    • Antiandrogen therapy/medications to treat benign prostate hyperplasia
    • Multi-vitamins

    Drugs believed to "cause, contribute to or aggravate" dry eye

    Source: Table 3, TFOS DEWS II Iatrogenic Dry Eye Report

    • Analgesics
      • Antirheumatic: Aspirin, Ibuprofen
      • Cannabinoid: Dronibinol, Tetrahydrocannabinol
      • Opioid: Buprenorphine, Fentanyl, Methadone, Morphine*, Opium*, Oxymorphone, Tapentadol
    • Anesthesia: Ether, Nitrous Oxide
    • Anticholinergic (antimuscarinic)
      • Antiarrythmic/Bronchodilating: Atropine, Diphenhydramine, Disopyramide, Homatropine, Ipratropium, Methscopolamine, Scopolamine, Tiotropium, Tolterodine
      • Antihistamine: Azelastine, Brompheniramine, Carbinoxamine, Cetirizine, Chlorpheniramine, Clemastine, Cyproheptadine, Desloratidine, Dexchlorphenamine, Diphenhydramine, Doxylamine, Epinastine, Fexofenadine, Hydroxyzine, Ketotifen, Loratidine, Olopatadine, Promethazine, Pseudoephedrine, Tripelennamine, Triprolidine
      • Antidepressant: Agomelatine, Amitriptyline, Bupropion, Chlomipramine, Cialopram, Desipramine, Doxepin, Duloxetine, Fluoxetine, Fluvoxamine, Imipramine, Mianserine, Mirtazapine, Nortripty, Paroxetine, Reboxetine, Sertraline, Tianeptine, Trazodone, Venlafexine
      • Anti-Parkinson's: Benapryzine, Benzhexol, Benztropine, Bornaprine, Levodopa, Methixine, Orphenadrine, Pamipexole, Procyclidine
      • Antipsychotic: Aiprasidone, Aripiprazole, Brompheniramine, Carbinoxamine, Chlorpheniramine, Chlorpromazine, Clemastine, Clozapine, Cyproheptadine, Dexchlorphiniramine, Fluphenazine, Haloperidol, Lithium carbonate, Olanzepine, Perphenazine, Promethazine, Quetiapine, Risperidone, Sulpiride, Thiethylperazine, Thioridazine Thiothixene, Trifluoperazine
      • Antispasmodic: Fesoterodine, Homatropine, Oxybutynin, Propantheline, Propiverine, Solifenacin, Tolterodine, Trospium
      • Decongestant: Oxymetazoline, Phenylephrine, Phenylpropanolamine, Pseudoephedrine, Xylometazoline
    • Antihypertensive
      • Adrenergic blocking: Acebutolol, Atenolol, Carvedilol, Labetalol, Metoprolol, Nadolol, Pindolol, Clonidine, Prazosin, Oxprenolol, Propranolol
      • Na+Cl- Co-transporter (diuretic): Bendroflumethiazide, Chlorothiazide, Chlortalidone, Hydrochlorothiazide, Hydroflumethiazide, Indapamide, Methyclothiazide, Metolazone, Polythiazide, Trichlormethiazide
    • Antileprosy: Clofazimine
    • Antimalarial: Chloroquine, Hydrochloroquine
    • Antineoplastic: Busulfan, Cetuximab, Cyclophosphamide, Docetaxel, Erlotinib, Gefitinib, Interferon, Methotrexate, Mitomicin C, Panitumumab, Vinblastine, Vertiporphin
    • Anxiolytic/hypnotic: Alprazolam, Diazepam, Eszopiclone, Lorazepam, Zolpidem, Zopiclone
    • Chelator/Calcium Regulator: Methoxsalen, Alendronate, Pamidronate, Risedronate
    • Depressant: Ethanol
    • Herbal and Vitamins: Isotretinoin, Niacin, Echinacea, Kava
    • Hormonal: Antiandrogen/Estrogen replacement: Alfuzosin, Doxazosin, Finasteride, Leuprorelin, Tamsulosin, Terazosin, Estrogen/progesterone, Medroxyprogesterone
    • Neurotoxin: Botulinum A or B

    A footnote about sources

    When I want to know the real skinny about most things related to dry eye, I go straight to TFOS DEWS II. This massive report, the result of a nearly three year project involving 150 specialists from around the world, is the bible of dry eye today. It is both an update, and a substantial expansion of the original report published in 2007. 

    I love TFOS DEWS II, because I no longer spend my time scouring PubMed for relevant studies, and struggling to determine which ones are most reliable and most relevant. That has all been done by top experts. They have combed through all the medical literature, evaluated everything according to stringest standards, written their reports and compiled the complete reference library of the best studies on each subtopic. It makes everything so much easier.

    One of the new features in the 2017 report that I was MOST excited about was the Iatrogenic dry eye report. Everything of note about medically induced dry eye has been pulled together in one place and summarized powerfully. This has never been done before! I learn so much every time I look up something new in it.

    Anyway, in all of our discussion about drying drugs (today) and drops (tomorrow) and surgeries (the next day), pretty much everything I write will be based on what I am finding in the Iatrogenic report. Here it is:

    TFOS DEWS II Iatrogenic dry eye report