Using data from the FDA Adverse Event Reporting System (FAERS), a recent study explored the risk of keratitis triggered by ophthalmic and non-ophthalmic medications.
Medications can lead to drug-related keratitis by either causing direct damage to the cornea or by reducing the cornea's immune barrier function and putting it at higher risk for infections and damage due to foreign bodies, the researchers explained in their article in Translational Vision Science & Technology. Typically, cases occur when ophthalmic medications are given frequently, for a prolonged period, or when medications are combined, often because a primary diagnosis has not been reached. Drug-related keratitis can also occur during treatment for a primary diagnosis, or after ocular surgery.
Noting that the study aimed to provide data to guide medication choices, the researchers note that to the best of their knowledge, the study is the first data evaluating he iatrogenic risk of drug-related keratitis associated with topical ophthalmic or systemic medications.
FAERS data from 2004 to 2023 were reviewed using disproportionality analysis and screening. From several methods of mining potential positive signals for keratitis—including reporting odds ratios (ROR) to quantify the risk of drug-related keratitis—the investigators found that 1,606 drugs posed a risk for drug-related keratitis. Dorzolamide, a commonly used ophthalmic drug, had an ROR of 3695.82, indicating a substantially elevated risk compared to other medications. Trazodone and belantamab mafodotin also demonstrated significant associations with keratitis, despite being non-ophthalmic medications.
Overall, the study identified 17 drugs that were significantly associated with drug-related keratitis. Seven of those were ophthalmic medications, including travoprost (ROR = 2287.27) and brimonidine (ROR = 2118.52). Ten were non-ophthalmic medications. The time to keratitis onset was more than twice as short for non-ophthalmic drugs compared to ophthalmic medications (141.02 vs. 321.96 days, respectively).
Of note, the researchers determined that benzalkonium chloride (BAK) was not the culprit for dorzolamide-induced keratitis in one patient. BAK is a preservative that has been linked to inflammation. In this study though, because the patient who had a reaction to dorzolamide continued to use timolol maleate (which also contains BAK) without experiencing keratitis, the investigators concluded that dorzolamide lead to this patient’s marginal keratitis, rather than the preservative in it.
With this data, the researchers hoped to add supplementary labeling information for drugs that potentially cause ocular adverse reactions.
A full list of author disclosures can found in the published research.
