If you've ever put in eyedrops, some of them have almost certainly spilled onto your eyelid or cheek.

The good news is the mess doesn't necessarily mean you missed. The bad news is that medicine you wiped off your face is wasted by design — and it's well-known to the drug companies that make the drops.

Eyedrops overflow our eyes because drug companies make the typical drop — from glaucoma drugs that cost hundreds of dollars to cheap over-the-counter bottles — larger than a human eye can hold. Some are so large that if they were pills, every time you swallowed one, you'd toss another in the garbage.

The waste frustrates glaucoma specialists like Dr. Alan Robin, whose patients struggle to make pricey bottles of drops last. He has urged drug companies to move to smaller drops — to no avail.

"They had no interest in people, their pocketbooks or what the cost of drugs meant," said Robin, a Baltimore ophthalmologist and adjunct professor at the University of Michigan Medical School.

ProPublica has been documenting the many ways money is wasted in health care. We've shown how hospitals throw out brand-new supplies, nursing homes flush tons of unexpired medication and drug companies concoct costly combinations of cheap drugs. Recently we described how arbitrary expiration dates for drugs cause us to toss safe and potent medicine.

Often, large swaths of the medical and pharmaceutical communities know about this waste — even about solutions to it — but do nothing. Those who end up paying the bill, in one way or another, are consumers.

Crucial eye medications to treat conditions like glaucoma can cost hundreds of dollars for a small bottle that lasts only a month, making the waste of even a drop a problem for low-income patients. Last year, drug companies brought in about $3.4 billion in the U.S. alone on drops for dry eyes and glaucoma drops, according to the research firm Market Scope.

Gregory Matthews said there have been times when he has run out of his $295 bottle of Azopt, a glaucoma medication, with a few days remaining before his refill and he has blamed himself. "You feel like you're doing something that's going to cause your blindness and it's because of you," said Matthews, 63, a teacher from Baltimore.

Smaller drops are feasible

Pharmaceutical companies have done research showing that it's possible to waste less and save consumers money. Some of that research has been around for decades.

Robin, for example, consulted in the early 1990s with Alcon Laboratories, one of the world's largest eye care companies, when its researchers developed a so-called microdrop. Patients, he said, were able to safely and effectively deliver the tiny drops, with nothing wasted. But instead of being a breakthrough, the innovation, he said, became a case study in how business interests trump patient needs.

Bill York recalls his bosses at Alcon coming to him in the early 1990s with a pressing request. Patients were complaining that some of the company's drops caused stinging and burning in their eyes. Could he find a fix?

York, head of the research lab at the company's Fort Worth, Texas, headquarters, knew one way to ease the irritation: Make the drops smaller. The size of eyedrops isn't regulated, he said recently. Some are over 50 microliters, more than twice what the eye can hold.

When drops are too big, the overflow runs down the face or drains into the body through the ducts in the corner of the eye, he said. This explains why you sometimes get the sensation of "tasting" eyedrops — they've entered your sinuses.

"If it spills out, it's just wasted," said York, who has a doctorate in pharmaceutical chemistry and is now retired. "It's not doing any good."

So his team created a 16-microliter drop — a microdrop — that was about a half to a third of the size of most drops on the market today, he said. The team used a standard bottle with a latex dropper tip that wouldn't cause injury if it touched the eye. Then they recruited 29 glaucoma patients to test the tiny drops. Glaucoma, a leading cause of blindness in the United States, is characterized by increased pressure in the eye, which can damage the optic nerve. Daily use of medicated eyedrops preserves sight by reducing the pressure.

The patients tried different formulations of the same medication in both micro- and regular drops, which were about twice as large, for a week at a time. The researchers tracked the patients' eye pressure and side effects, such as burning, stinging, itching and dryness.

Their results were conclusive: Microdrops worked as well as larger drops to lower eye pressure. They also reduced some of the uncomfortable side effects of larger drops. And all the patients preferred using them.

York and two of his Alcon colleagues published their results in 1992 in the American Journal of Ophthalmology. Robin, who consulted on the research, was the principal investigator.

"The microdrop delivery system worked," York said recently. The drop "was manufacturable. It reduced stinging and the amount of drug needed to produce the same biologic effect. Excess drug draining out of the eye would be significantly reduced."

Would smaller drops lower sales?

But his innovative solution ground to a halt when it came to getting it on the market.

Back in the early 1990s, Jerry Cagle was the head of product development at Alcon. Cagle, who has a doctorate in microbiology, retired in 2008 after 32 years at the company. He said the microdrop project failed because it raised too many questions — all of them about profits.

First, would competitors in the cutthroat eye care business undermine the project? One time, Cagle recalled, Alcon wrapped one of its bottles in foil to reduce evaporation, extending the life of the product. A competing company started a rumor that Alcon's drops needed the foil because they were toxic. Alcon had to remove the foil. "No good deed goes unpunished," Cagle said.

Second, if Alcon reduced the drop size on this product, would it have to do the same on the company's other eyedrops?

And maybe most crucially, how would the microdrops affect sales? Microdrops, Cagle recalled, had "the potential to increase the use-life of a bottle by a factor of two," which could cut sales in half. But if they raised the price on the bottle to recover revenue, Cagle said, "then what's a competitor going to say? 'Look at Alcon's product. It's twice as expensive as ours.' "

Alcon would also have to get Food and Drug Administration approval. Company-funded studies would need to prove to the agency that the smaller drop was just as effective as a larger drop.

So the project was killed, Cagle recalled, doomed by the cost of bringing the microdrops to market, combined with the risks of whether they would sell. "I'm a believer in small drops, don't get me wrong," Cagle said. "If this had been an innovation we thought would have increased Alcon's sales, I think it would be in the marketplace today."

Novartis, which now owns Alcon, didn't want to talk about the microdrop study. When asked about the drop size, a spokesperson said the drops include a "margin of safety" to ensure patients get enough of the drug in their eyes.

Robin recalled a different response in the 1990s when he urged Alcon executives to pursue the microdrop. It was, he said, like asking your wife if you could leave town for your anniversary or her birthday. "It was a dead issue," Robin said. "They would say, 'It's not profitable. We're going to sell less drugs.' Very simple. Bottom line."

Drugmakers have long known drops were oversize

Twenty-five years later, things haven't changed. Those in the eye care industry — doctors, pharmaceutical officials, researchers — know that eyedrops are much larger than the eye can hold.

But there's little focus on the waste. Dr. Michael Repka, spokesman for the American Academy of Ophthalmology, said the drops have been larger than the eye's capacity for the three decades he has been in practice. While the focus has been on drop administration and ensuring patients can get refills, he said, the industry should be looking at drop size.

You might think the FDA would intercede, but the agency's mission is the safety and efficacy of drugs, not prices or indirect costs due to waste.

Since Alcon's mothballed research in the early 1990s, other studies have similarly found that most drops on the market are larger than necessary. A 2006 study published in the Journal of Ocular Pharmacology and Therapeutics, for example, said 15-microliter drops are as effective as large drops. "Smaller drops would be preferable to minimize systemic exposure and spilled or wasted medicine," the study said.

Two of its authors worked for the pharmaceutical giant Allergan, which also funded the study. Allergan still doesn't make any drops that are 15 microliters or smaller. The company declined to comment.

Another study published in May in the journal BMC Ophthalmology said "a significant portion of an eyedrop is wasted."

Internal drug company documents and depositions unearthed in a recent court case in Illinois also suggest that companies have long known their eyedrops are bigger than human eyes can absorb.

A 2002 Bausch & Lomb memo said dropper tips "deliver drops which exceed that of which the physiology of the eye can retain."

A 2011 Pfizer memo said: "The drop size is not a medical dosing issue because the human eye can only absorb 7 (microliters) of fluid." Common drop sizes are between 25 and 56 microliters, the memo added.

And in a 2014 deposition, a scientist from Allergan acknowledged that the company studied glaucoma drops of 5, 10, 15, 20 and 30 microliters in size and found no statistically significant difference in the ability of the drops to reduce eye pressure.

None of the drug companies wanted to discuss these documents or why they haven't pursued a smaller drop.

Even a drug industry consultant, Gary Novack, said it would be ideal to have a smaller drop with a higher concentration of medicine. But Novack, a pharmacology expert who helps companies shepherd products to market, doesn't believe reducing the size of drops would lower health care costs. The drug companies, he said, would "acclimate," raising prices by charging by dose instead of volume.

Big drops strain pocketbooks

It isn't hard to find patients who are feeling the cost of this waste.

David Zinke, 67, lamented on Facebook that he couldn't afford the $185 per month drops his doctor had just prescribed.

He was shocked to hear about microdrops. He always thought "a drop was a drop." Zinke said he was getting by on his Social Security plus what he made by selling fudge and driving for Uber in Tucson, Ariz., clearing about $1,500 a month. His budget doesn't cover the brand-name drug, so every day he uses three less expensive bottles of drops.

"If we could deliver it in a smaller and more appropriate way," he said, "then that little bottle of 2.5 milliliters would last me two months instead of one."

Matthews, the teacher in Baltimore who fears running out of his drops, carefully puts a single drop of Azopt into each eye twice a day to preserve his remaining eyesight. His glaucoma has left him almost completely blind in one eye and partially blind in the other.

The drops allow him to continue to work as a teacher and watch his beloved Baltimore Orioles. Azopt is made by Alcon. Matthews has good insurance, so he doesn't pay the $295 sticker price. But he can't get a refill until after the insurer figures his supply should have lasted, so it's critical not to waste a single drop.

But no matter how hard he tries, the drug gets wasted. Each drop is more like a milky "gob" that collects in the corner of his eye. "Sometimes I feel like I'm wiping half of it out," he said.

As he talked about the size of eyedrops, Matthews grew more irritated. "This whole blind thing takes some getting used to," he said. "If the maker of the medicine isn't really looking out for me, that bothers me."


ProPublica is a nonprofit newsroom based in New York. You can follow Marshall Allen on Twitter: @marshall_allen

Copyright 2017 ProPublica. To see more, visit ProPublica.

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