Medications that may cause or worsen symptoms of dry eye disease (DED) are numerous, and particularly include antidepressants and various glaucoma therapies. Instead of observing the effects of entire drug classes, researchers in a new study looked at how individual medications may pose a risk for presentations of dry eye. 

The cross-sectional study included 79,606 patients from the Netherlands (aged 20-97 years, 59% female). Dry eye symptoms and severity were assessed using the Women’s Health Study three-question dry eye questionnaire. Medication use among patients was specified, and each medication was given a code using the Anatomical Therapeutic Chemical (ATC) classification system (researchers excluded 1st and 2nd classifications, as they were too broad). Medications not used by at least 200 participants were also excluded from the analysis. Participants provided data at baseline between 2006-2013 and during a follow-up assessment between 2014-2017. 

At least one type of medication was being used by 53% of participants, 33% of which were experiencing DED symptoms. Of the group using no medication, just 26.1% experienced dry eye. Drugs for peptic ulcer and GORD were most strongly associated with DED at ATC 3rd level, as well as medications for functional gastrointestinal disorders. Level vitamin B12 and folic acid were also associated with DED at this level. 

At ATC 4th level, patients using proton pump inhibitors (PPIs) held the highest risk. Synthetic anticholinergics and other antiepileptics also increased risk at the 4th level. At ATC 5th level, omeprazole, pantoprazole and esomeprazole took the win, with mebeverine and ispaghol trailing close behind in terms of DED symptom risk.

“This study found PPIs to be the most significant independent risk factor of dry eye symptoms of all commonly used medications,” the researchers wrote in their paper. “PPIs are frequently prescribed, with 8.3% of our study population reporting PPI use, amounting to a population attributable fraction of dry eye symptoms of 1.9%.” Stomach ulcers are also highly associated with dry eye.

For some patients, taking certain medications actually reduced dry eye risk. Patients diagnosed with depression on antidepressants had a lower risk than those who were diagnosed but unmedicated. Those on selective serotonin or non-selective monoamine reuptake inhibitors may also experience a decreased risk of DED. In contrast to previous studies that observed drug classes as a whole, antidepressants were not shown to increase risk, and neither did antihypertensives, but antiglaucoma drugs and anticholinergics did.

You should inform your patients taking PPIs of the possible DED risk and ask those who present with DED symptoms if they are taking this medication or others. Medication use should be assessed in every patient who walks into your practice, especially those with such a complex and multifactorial disease as dry eye.

Wolpert LE, Snieder H, Jansonius N, et al. Medication use and dry eye symptoms: a large, hypothesis-free, population-based study in the Netherlands. Ocular Surface. January 29, 2021. [Epub ahead of print].