By: Dr. Benjamin Nicholas, Berks Eye Physicians & Surgeons
Over the past few months, you may have heard some concerning stories about devastating side effects from artificial tears. These eyedrops are meant to supplement a deficient tear film and clear mucus away from the ocular surface to alleviate the symptoms of a dry eye. Dry eye itself is extremely common with an estimated prevalence of greater than 16 million patients back in 2017 (1), and these over-the-counter eye drops are almost universally recommended by eye doctors on account of their good safety profile and effectiveness. “You can never OD on an artificial tear,” said one of my mentors. So, what’s all the fuss?
Artificial tear basics
Just as with any other medication, the manufacture of eye drops may involve the introduction of impurities or even contaminants. But unlike other medications, artificial tear products are not subjected to the same rigorous review process required by the FDA for other new medications. The reason for this is that the FDA established in 1988 that new artificial tear products may be fast-tracked to market provided they meet a series of specific requirements (such as with regards to their ingredients). Provided these conditions are met, they are “generally recognized as safe and effective” (2).
Additionally, artificial tears come in two broad categories: preserved and preservative-free. Preservatives can be helpful to have in an artificial tear formula as it lengthens the shelf-life of the drop and helps inhibit the growth of bacteria. Unfortunately, preserved eye drops also irritate the surface of the eye, particularly if they are used frequently (3). For this reason, many eye doctors will recommend using preservative-free artificial tears to treat dry eye.
So why all the recalls?
As of the writing of this article, there are have been three manufacturer recalls affecting artificial tears. All eye drop products produced by the companies EzriCare, Delsam Pharma, and Akorn have been recalled. You should no longer be able to find them on the shelves, but certainly avoid them if you should see them.
The drops produced by EzriCare and Delsam Pharma (both owned by the same manufacturer, Global Pharma) were linked with an outbreak of a multidrug-resistant version of the bacterium pseudomonas aeruginosa. This particular bacterium can cause dangerous infections of the eye which, left untreated, can cause severe vision loss or even penetrate through the front of the eye to spread within the globe itself. As of the time of this writing, 81 patients across 18 different states have been found to be infected by this particular organism. Most of the affected patients reported using artificial tears, sometimes multiple types. Many of these patients – though we are not told just how many – resided in four different healthcare facility “clusters,” and the only common artificial tear product used across all four of these clusters was that produced by EzriCare. 14 of the 81 patients developed vision loss from these infections, 4 required surgical removal of the eye, and 4 died within 30 days of identification of the bacterium (3).
So how did that happen?
While the bacteria that caused this outbreak were found in open bottles of EzriCare artificial tears, subsequent testing of unopened bottles also revealed contamination, suggesting possible introduction of the bacteria during the manufacture process (4). The FDA investigated the facility in India where these artificial tears were produced and noted, in a heavily redacted report, multiple deficiencies with regards to sterility (5).
When I first heard these dramatic stories, I was shocked. Not only are artificial tears almost universally safe, but most of the devastating effects that were reported would usually be noticed by a patient very early in the infection process. Patients report to us frequently with eye infections from a variety of sources. They generally come to their eye doctor promptly – as they know something is wrong – and they can usually be treated successfully. An eye infection that reaches the point of requiring removal of the eyeball, or even death, is extremely rare.
Because a significant part of this outbreak was noted among healthcare facilities, it is possible that patients with the most severe adverse effects may have been those residing in such facilities. Such individuals may have difficulty informing their physician they have an eye problem, particularly if they have suffered a stroke or have dementia. Even those that can advocate for themselves may not have ready access to an eye care specialist at their facility who can provide an accurate diagnosis and appropriate treatment in a timely fashion.
All of the above could have produced a “perfect storm” that might allow a contaminated eye drop to wreak havoc due to a delay in diagnosis and treatment that is not typically experienced by the general population outside of healthcare facilities.
Artificial tears are still generally safe
While the issues with EzriCare artificial tears were quite dramatic, they do not represent the artificial tear industry as a whole.
Preservative-free artificial tears work tremendously well. I have recommended them to many of my patients, members of my own family use them, and I use them myself occasionally. However, it is important to respect the use-by date printed on the product, and to avoid using an eye drop you believe may be contaminated. In particular, this includes usage of an open bottle that has already been used by someone else.
If you’d like to take even greater precautions, I would also advise adhering to well-established brands. When a new artificial tear comes out, wait a few months to make sure it’s not generating any headlines before you put it in your own eye.
What about Akorn?
It is true that Akorn Pharmaceuticals recently recalled many of their eyedrops, but this was unrelated to any concerns for sanitation or infections. Akorn filed for bankruptcy this past February, and in the process of shutting down operations they ended their “Quality” program which worked to ensure medications were produced without impurities or contaminants. Without the Quality program, Akorn is no longer able to verify the safety of their medications. Thus, they issued a voluntary recall of over 70 of their medications. This was a wide-ranging move affecting many varieties of their drugs, from anti-seizure medications to eyedrops (6).
- Farrand, K.F., Fridman, M., Stillman, I.O., Schaumberg, D.A. (2017). Prevalence of diagnosed dry eye disease in the United States among adults aged 18 years and older. American Journal of Ophthalmology, 182, 90-8.
- Food and Drug Administration. (1988). Ophthalmic Drug Products for Over-the-counter Human use; Final Monograph (OTC Monograph M018). Available from https://www.accessdata.fda.gov/drugsatfda_docs/omuf/OTC%20Monograph_M018-Ophthalmic%20Drug%20Products%20for%20OTC%20Human%20Use%2004.04.22.pdf
- American Academy of Ophthalmology. (2019). Ocular Pharmacotherapeutics. In Basic and Clinical Science Course (Section 2). Brar, V.S., Law, S.K., Lindsey, J.L., Mackey, D.A., Schultze, R.L., Silverstein, E., Singh, R.S.J. (eds.).
- Centers for Disease Control and Prevention. (2023, March 21). Outbreak of extensively drug-resistant Pseudomonas aeruginosa associated with artificial tears. https://www.cdc.gov/hai/outbreaks/CRPA-artificial-tears.html
- Department of Health and Human Services. (2023, March 2). Form FDA 483 Inspectional Observations. https://www.fda.gov/media/166739/download
- Food and Drug Administration. (2023, May 4). Update – Akorn issues voluntary nationwide recall of various human and animal drug products within expiry due to company shutdown. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/update-akorn-issues-voluntary-nationwide-recall-various-human-and-animal-drug-products-within-expiry