Can eye drops kill you? Part 2: avoiding “Buyer’s Remorse.”
We’ve all heard the term: “Buyer Beware” - though in the world of health safety and in particular, eye safety, should a buyer have to beware? The short answer is “maybe.” I hope by choosing your dry eye specialist with care, we can help eliminate “Buyer’s Remorse.”
Regener-Eyes has been marketed as a “biologic” artificial tear, said to contain some of the proteins and materials found in a pregnant womb. Another company, M2 Biologics followed suite, creating StimulEyes. Regener-Eyes makes a “prescriptive” (or “Pro”) strength (said to require an actual prescription to purchase and requiring refrigeration after opening) and a “Lite” version (said to not require refrigeration and said to not have preservatives). These companies came under the scrutiny of the FDA as unapproved for any treatment – though Regener-Eyes claims to have been approved by the FDA as an Over-The-Counter (OTC) product deemed “generally safe and effective for its intended use.” Upon further research, there is an FDA online service noting the ingredient in the Regener-Eyes product is “Glycerin,” which I will note is not considered a biologic and can be found in other OTC artificial tears (in a very dilute concentration). Whether any of these products contain a biological agent remains a mystery, as the companies have so far refused to clarify what else is in them. I should note that at present, I am unaware of any poor outcomes associated with the use of any Regener-Eyes or StimulEyes products. Because of the lack of preservative (or refrigeration) in a simple dispensing bottle, I found the risk of recommending these products to be too close to the range of problems caused by the drops I covered in my last post and will repost an article I found that helps underscore these risks, along with a simple diagram of unapproved vs approved dispensing bottles for artificial tears (and other eye drops), here:
“Dry Eye Foundation continues to warn against the use of unverified and unsafe eye drops
May 12, 2023
From ingredients that should not be included to ingredients that should be but are not, and improper storage and manufacturing, numerous eye drops have raised safety concerns.
(Image Credit: AdobeStock/Geparda)
The Dry Eye Foundation is warning against the use of certain eye drops marketed for use in the United States.
From ingredients that should not be included to ingredients that should be but are not, and improper storage and manufacturing, Sandra Brown, MD, Dry Eye Foundation board member and medical advisor, has been sounding the alarm since the beginning of 2022.
In April 2022, the Dry Eye Foundation alerted the FDA to 2 brands of unapproved biologic eye drops being distributed commercially as prescription drugs.
“We've been banging this drum since first quarter, early second quarter of 2022,” Brown said. “The exact safety issue is that you cannot put a multidose eye drop that does not contain preservative in a bottle.”
Brown explained the reasoning behind this sentiment, in that preservative-free eye drops need to be put into a bottle specifically designed for them.
“Recently, thankfully, they've developed a special type of dropper that can be used with preservative-free eyedrops,” she said. “You can usually, easily, identify the bottle because it’s got kind of a funny sort of square cap on it [and] is called a multi-dose preservative-free dropper, an MDPF dropper. You cannot take a non-preserved eye drop and put it in a standard bottle. Because it does not prevent backwash.”
Brown described backwash as when the tip of the dropper becomes contaminated, then you let go of the squeeze, the bottle sucks contaminated liquid back into the bottle.
This is one of the reasons preservative-free bottles cannot be put into ordinary bottles, as ordinary bottles do not protect against backwash, according to Brown.
The Dry Eye Foundation includes a list of products that it has concern over on its website. Currently, there are more than 30 brands and even more products that the foundation has listed as an “orange level alert.”
(Image Courtesy Dry Eye Foundation)
The foundation defines an “orange level alert” by the potential for non-sterility of the eye drops because it is an unregistered or unlisted drug, or it is registered or listed, but has red flags. For instance, eye drops that are registered with the FDA contain ingredients not permitted in OTC eye drops or not recognized as preservatives. While some are packaged in conventional multi-dose bottles despite being preservative-free. Which was an issue seen with EzriCare eye drops.
EzriCare eye drops are included in the foundation's “red alerts” which are CDC Health Alerts, FDA Public Safety Notifications, and Class 1 Recalls pertaining to over-the-counter eye drops.
EzriCare eye drops are a product from Global Pharma Healthcare, where an FDA inspection found dozens of contamination issues in a facility in India.
These eye drops were responsible for an outbreak of VIM-GES-CRPA, a rare strain of extensively drug-resistant Pseudomonas aeruginosa, which has not before been identified in the US according to the CDC.
Brown stressed the importance of the unique genetic signature of this strain.
“That's the key thing is that it has a unique genetic signature. and the fact that it's caused serious infection in people from one end of the country to the other, and it has a unique genetic signature means it came over on the boat,” said Brown. “So yes, it's a problem that it was a standard eye drop bottle with no preservative, but it also was contaminated during manufacture … one of the things that [preservatives] are supposed to be able to kill [are] pseudomonas.
You can view a complete list of the alerts and products to be wary of online.
Brown listed some of the ingredients to look out for; “Anything that says, ‘contains vitamins, MSN, amino acids, honey.’ Those are common ingredients that are not allowed in an over-the-counter eyedrops.”
The ease of purchasing eye drops online thanks to websites like Amazon are a greater reason for concern and awareness, said Brown. Consumers need to be sure to “know your seller” when purchasing online.
“It is a buy-at-your-own-risk kind of approach. It allows these products to reach a really wide audience. So, before Amazon took the entry care listing down, it had close to 2500 reviews with a 4.5 star review,” said Brown.
To be safe on purchases, Brown encourages using DailyMed to verify the product.
“What I do say is step one, go to DailyMed, if It's not listed on DailyMed, do not buy it,” she said. “But understand that just being listed on DailyMed, does not mean it's alright.”
Becoming educated on the process of FDA protocols and the ingredients that are included in the products that are being purchased and used are one of the most important acts of self-awareness according to Brown.
“I think my message to ophthalmologists is that EzriCare has taught us that we have to pay more attention to our patients over the counter products,” Brown concluded. “It is time to start looking at them. So have the patients bring them in, dump out their bottles. Check to be sure
they are not using something weird, or, you know, some off-price brand. Especially if the patient's having some strange problem you cannot get on top of, consider whether or not it is actually their over-the-counter products.””
Another journalist reported on the so-called biologic drops here: This is a MedPage Today story.
https://abcnews.go.com/Health/wary-unproven-eye-drop-treatment-amniotic-fluid-fda/story?id=98836159
“Be wary of unproven eye drop treatment with amniotic fluid, FDA says
The FDA says there is no assurance the products are safe or effective.
By Kristina Fiore | MedPage Today
FDA issues warning over amniotic fluid eye drops
The Food and Drug Administration has pushed for regulation around the marketing and sale of birth tissue-derived stem cell products for dry eye disease.
In its ongoing battle against companies selling unapproved stem cell products, the FDA issued a safety communication earlier this month about amniotic fluid eye drops being improperly marketed for dry eye disease.
The communication links to earlier letters to two manufacturers -- makers of Regener-Eyes and StimulEyes -- warning that the products would need an approved Biologics License Application (BLA) to stay on the market, or health care providers would need an investigational new drug (IND) application to deliver them to patients.
"There are no assurances that the products are safe and effective for any disease or condition," FDA said in its safety communication, adding that there are "currently no FDA-approved amniotic fluid eyedrops to treat, mitigate, or cure eye diseases or conditions."
MORE: Death toll linked to contaminated eye drops rising as more report vision loss
Both products appear to be readily available for sale on the internet, with plenty of options on Google Shopping. Although StimulEyes maker M2 Biologics states on its homepage that online ordering of the product is currently unavailable, the product appears to be available for purchase through other channels.
Neither Regener-Eyes CEO Dr. Randall Harrell nor M2 Biologics returned a request for comment.
It's not clear if the companies made other changes to their products or their marketing following the FDA's earlier letters. The original "untitled" letter to Harrell and Regener-Eyes from October said the company made claims on its website that it was a "biological product" composed of "placental-derived biomaterials" and used for the treatment of dry eye disease.
The untitled letter to M2 Biologics sent in November said its website claimed StimulEyes was a "regenerative medicine" product also used for treatment of dry eye disease.
In both cases, the FDA said the products appeared to be a drug and a biological product and would need a valid biologics license to be marketed.
"Your product is not the subject of an approved biologics license application (BLA), nor is there an IND in effect for your product," the FDA stated in both letters.
The FDA has been getting tougher on "birth tissue" companies, which market products that allegedly contain stem cells and other biological materials that are derived from the placenta and umbilical cord. The agency has argued that these are biological products that need to be regulated as such.
Leigh Turner, executive director of the bioethics program at the University of California Irvine, who has long been tracking stem cell companies, said that while "hundreds" of businesses sell such allogeneic birth tissue-derived stem cell products, a "much smaller number of companies advertise purported 'regenerative' amniotic fluid eye drops for dry eye disease and other indications."
"The problem with such commercial activity is that such companies haven't tested their products in controlled clinical trials and the safety and efficacy of such amniotic fluid products in the treatment of individuals with dry eye disease and other diseases have not yet been established," Turner told MedPage Today. "These untested or inadequately tested products pose risks to patients, as the recent public safety notification issued by the FDA notes."
In its letter to Regener-Eyes, FDA noted the company described its product as an "acellular" biological product, meaning it does not contain stem cells, Turner said, adding that it's "not clear what businesses are claiming when they assert such products have regenerative properties."
"It appears to be another example of using the hype and buzz associated with regenerative medicine to sell purported treatments," Turner said.
Paul Knoepfler, of the University of California Davis, who has also been tracking the stem cell industry, said that these products still could contain growth factors and other substances that could have activity in the eyes.
"The drops likely contain hundreds of different fetal proteins and other substances, which don't necessary just do helpful things, so there are definite risks," he told MedPage Today.
He warned that such possible tissue changes "may not be entirely reversible after stopping the drops. We just don't know."
Knoepfler added that any drug placed into the eye could end up "in systemic circulation so there could be risks outside of the eye. I'd also worry about risks of infection."
"There are good reasons to treat these products as drugs and require robust clinical trial data before marketing," he said.
Turner noted the FDA's use of untitled letters to the two companies may not have enough teeth to force any real change, especially as the products appear to be readily available for purchase online.
"More robust regulatory responses are likely needed to curtail such activity," he said.
In its notice, FDA said health care providers should report any adverse events associated with amniotic fluid eye drops to its MedWatch program.”
To schedule an appointment with Dr. Jaccoma, call Excellent Vision at either of these two dry eye offices:
(1) 155 Griffin Rd, Portsmouth, NH 03801 (603) 574-2020
(2) 3 Woodland Rd, STE 112 Stoneham, MA 02180 (near Boston) (781) 321-6463