Using secondary analysis from the DRy Eye Assessment and Management (DREAM) study, a new paper published in The Ocular Surface found associations between certain systemic medications and more severe dry eye disease (DED).
Give me some background first.
The DREAM study (NCT02128763), originally published in 2018, enrolled participants from 27 dry eye centers across the United States in a prospective, multicenter, double-masked, randomized clinical trial assessing the efficacy and safety of oral omega-3 supplementation for the treatment of DED.
That study found that patients receiving omega-3 supplements did not experience better outcomes than patients who received placebo.
Let’s talk study details.
The DREAM study included conjunctival staining scores, corneal fluorescein staining scores, tear film break-up time (TBUT), anesthetized Schirmer’s tests, and participant history of systemic medication use at baseline.
Using this data, the study authors were able to categorize the systemic medications into 14 classes:
- Antidepressants
- Antihistamines
- Aspirin
- Corticosteroids (e.g., prednisone, methylprednisolone, dexamethasone)
- Diuretics
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Proton pump inhibitors (PPIs)
- Statins
- Vitamin D3
- Medications for diabetes mellitus
- Medications for hypertension (e.g., hydrochlorothiazide, furosemide, lisinopril)
- Medications for hypothyroidism (i.e., levothyroxine)
- Medications for migraine (e.g., sumatriptan, butalbital)
- Medications for seizure (e.g., gabapentin, lamotrigine)
Medications used by fewer than 10 participants were excluded from the analysis.
So what was analyzed in this secondary analysis?
Using generalized linear models, the study authors compared the DED signs and symptoms of the DREAM study participants with their associated systemic medication use.
Did they adjust for any other factors?
Yes—age, gender, race, smokers vs non-smokers, and comorbidities like Sjögren’s disease, rheumatoid arthritis, and facial rosacea.
They also included depression, since the DREAM study found an association between depression and more severe DED.
And what was found?
Based on the comparison in both univariable and multivariable analysis, corticosteroids were the worst offenders when it came to more severe signs and symptoms of DED:
- higher composite signs severity score (0.72 vs. 0.49; p=0.008)
- lower average TBUT (2.4 vs. 3.6 seconds; p=0.02)
- lower Schirmer test scores (6.1 vs. 9.9 mm/5min; p=0.03)
Patients prescribed medications for seizure had a higher composite signs severity score, while users of antihistamines, aspirin, and vitamin D3 had worse average TBUT. Finally, users of vitamin D3 had worse scores for meibomian gland dysfunction (MGD).
Interestingly, users of diuretics actually had better MGD scores.
Tell me more.
Although ophthalmic corticosteroids are available and effective for DED treatment, oral corticosteroids have known ocular effects, including steroid-induced glaucoma and cataracts.
The authors noted that few studies have investigated the effect of oral corticosteroids on DED.
Expert opinion?
The study authors specifically noted the vitamin D3 results, which conflicted with the results of previous studies. They suggested that the worse TBUT scores in the users of vitamin D3 among the DREAM cohort could be attributed to vitamin D3 deficiency, which is a known contributing factor to higher rates of DED.
Limitations?
The study was limited to the DREAM cohort, which means among other things that these results cannot be generalized to patients with anything less than moderate DED.
Additionally, while they adjusted for systemic diseases known to be associated with DED, none of these results are causative—only correlative.
Take home.
Ultimately, the study authors noted, “Understanding how medication use may contribute to DED severity may help identify individuals who experience more severe DED from use of systemic medications and improve the clinical care of DED patients by suggesting therapeutic options (e.g., medication discontinuation) to alleviate disease progression.”
However, they concluded, further study is needed.