The Dry Eye

Wet cheekbones: Is it time to move away from eye drops?

Several alternatives may reduce the burden of preservatives on the ocular surface while potentially improving adherence to therapy.

There is this really cool “meeting before the meeting” that occurs on the Thursday of ASCRS and AAO week each year. The Ophthalmology Innovation Summit is the brainchild of Emmett Cunningham, a uveitis specialist who now spends his days nurturing startups. Many of the cutting-edge tech, device and pharma companies that surround our practices come together under the OIS tent to present their latest ideas to an audience that includes various and sundry “masters of the universe” types looking for their next blockbuster investment. Frankly, it is a bit pricey, but if you can sneak away on the day before Subspecialty Day, it is a fascinating look into what may be coming to your office.

Or going away, as the case may be this year.

No fewer than three presentations dealt with the scourge of preservatives in our topical therapies. We all know that benzalkonium chloride (BAK) is a classic double-edged sword. Not only is it a highly effective antimicrobial preservative that extends the useful life of a bottle of eye drops, but in some cases (eg, glaucoma) the presence of BAK may actually enhance penetration of the active ingredient. However, anyone who spends even 1 minute thinking about the ocular surface knows that repeated exposure to BAK often leads to chronic redness and inflammation, either inciting or worsening dry eye disease. Minimizing or eliminating BAK exposure makes our jobs easier.

Was it TheraTears (Akorn) or Refresh Plus (Allergan) that introduced the eye world to preservative-free eye drops? No matter. Sometime in the 1990s, we started to see unit dose dispensing of eye drops that were free of all preservatives. These are now ubiquitous, especially in dry eye. Pretty much every artificial tear of note has a preservative-free version, and all three of our on-label DED therapeutics (Allergan’s Restasis, Novartis’ Xiidra and Sun’s Cequa) are predominantly provided in dropperette form. We face a maddeningly meager selection of other medications in non-preserved form. Why can’t I find a preservative-free steroid? Making matters worse, the preservative-free medicines that are available are either buried below tier 5 or produced by junior varsity companies that have trouble staying in the game.

It makes you wonder if there was a way to get the benefit of BAK in the bottle (long, sterile shelf life) without the pain of having to deal with BAK on the ocular surface. As it turns out, there is. Vance Thompson and his team have created a new company around the concept of removing BAK from an eye drop on its was out of the bottle. TearClear employs a super-duper secret filter that selectively traps the BAK molecules before the drop reaches the tip of the bottle. Theoretically, any medication that does not employ BAK to traverse the ocular surface can be dispensed from a TearClear bottle. My bet is that TearClear is the transformative product of OIS/AAO 2019.

Unless we are at the beginning of the end of the eye drop age.

When you think about it, eye drops have been the preferred way to get medicine onto and into the eye for centuries. Cleopatra was said to put atropine in her eyes; large pupils have been shown to enhance attractiveness. (As an aside, maybe her induced presbyopia was the reason hieroglyphics are so big.) While we can disagree on the magnitude of the problems, it is clear that a significant percentage of our patients are more effective at lubricating their cheekbones than they are at medicating their eyes. Heck, there are studies that show anywhere from 25% to 50% of bottles end up contaminated. Each eye drop contains anywhere from 35 µl to 45 µL of fluid, likely dousing the ocular surface with more drug than it can absorb in addition to a bunch of BAK.

Four companies went big at AAO on a “no eye drops” approach to treating eye diseases such as dry eye, two of which presented at OIS. Eyenovia calls its technology “piezo print.” From what I saw at OIS, a fine mist is gently sprayed onto the cornea. The Optejet dispenser delivers 8 µL of drug, most likely in non-preserved form. Kedalion AcuStream similarly delivers approximately 10 µL of drug in a thin stream of fluid that makes contact with the cornea before one can blink. They, too, anticipate using preservative-free medicines.

One can readily see obvious applications for both of these systems. In the office, your techs can apply dilating “drops” much more efficiently and effectively, likely saving you money in the process. Elderly and infirm patients are also super candidates for an automated system that is accurate and easy to use. A phone app could track adherence. How about all of the parents whose sanity you have saved, and children saved from the psychological trauma of getting drops from those same parents? Think micro-dose atropine for myopia progression mitigation on the young side, and glaucoma treatment on the old. I see no reason why these would not work; their success in the real world will likely depend entirely on cost.

Another alternative to eye drops is to remove the entire treatment process from the hands of the patient. I have made no secret of my enthusiasm about the drug-eluting punctal plugs developed by Ocular Therapeutix. Sydney Tyson, MD, is an early advocate for moving toward a dropless cataract experience for our patients. He was a driving force behind Dextenza, which delivers non-antimicrobial preserved dexamethasone in a slow-release fashion in the perioperative period. To be honest, this is probably the least interesting application for a drug-eluting plug for DED docs. Dry eye steroids, immunomodulators, antihistamines, you name it — as long as you place the plug properly, you have 100% adherence to treatment. Side effects or complications? Just remove the plug.

Of course, the truly outside-the-box thinkers are not only doing away with drops, they are not even putting medicine on the eye. It should come as no surprise that Michael Ackerman of TrueTear (Allergan) fame has launched a company that seeks to treat DED with a medicine that is applied to the trigeminal nerve in the nose. OC-01 is a preservative-free nasal spray that contains a receptor agonist that activates the parasympathetic trigeminal fibers. Once activated, these nerves stimulate the production of tears from the entire lacrimal functional unit (lacrimal glands, meibomian glands, goblet cells). The ultimate ocular surface treatment may not only do away with drops, it may not even be applied to the ocular surface.

Is the age of eye drops over? Hardly. However, OIS and the AAO meeting introduced us to several alternatives that may allow us to reduce the burden of preservatives on the ocular surface while potentially improving adherence to therapy. It is highly likely that all of the examples above will find their way into our practices.

(I do not have a relationship with any of the companies mentioned above. Weird, huh?)

Disclosure: White reports he is a consultant to Allergan, Shire, Sun, Kala, Ocular Science, Rendia, TearLab, Eyevance and Omeros; is a speaker for Shire, Allergan, Omeros and Sun; and has an ownership interest in Ocular Science and Eyevance.

There is this really cool “meeting before the meeting” that occurs on the Thursday of ASCRS and AAO week each year. The Ophthalmology Innovation Summit is the brainchild of Emmett Cunningham, a uveitis specialist who now spends his days nurturing startups. Many of the cutting-edge tech, device and pharma companies that surround our practices come together under the OIS tent to present their latest ideas to an audience that includes various and sundry “masters of the universe” types looking for their next blockbuster investment. Frankly, it is a bit pricey, but if you can sneak away on the day before Subspecialty Day, it is a fascinating look into what may be coming to your office.

Or going away, as the case may be this year.

No fewer than three presentations dealt with the scourge of preservatives in our topical therapies. We all know that benzalkonium chloride (BAK) is a classic double-edged sword. Not only is it a highly effective antimicrobial preservative that extends the useful life of a bottle of eye drops, but in some cases (eg, glaucoma) the presence of BAK may actually enhance penetration of the active ingredient. However, anyone who spends even 1 minute thinking about the ocular surface knows that repeated exposure to BAK often leads to chronic redness and inflammation, either inciting or worsening dry eye disease. Minimizing or eliminating BAK exposure makes our jobs easier.

Was it TheraTears (Akorn) or Refresh Plus (Allergan) that introduced the eye world to preservative-free eye drops? No matter. Sometime in the 1990s, we started to see unit dose dispensing of eye drops that were free of all preservatives. These are now ubiquitous, especially in dry eye. Pretty much every artificial tear of note has a preservative-free version, and all three of our on-label DED therapeutics (Allergan’s Restasis, Novartis’ Xiidra and Sun’s Cequa) are predominantly provided in dropperette form. We face a maddeningly meager selection of other medications in non-preserved form. Why can’t I find a preservative-free steroid? Making matters worse, the preservative-free medicines that are available are either buried below tier 5 or produced by junior varsity companies that have trouble staying in the game.

It makes you wonder if there was a way to get the benefit of BAK in the bottle (long, sterile shelf life) without the pain of having to deal with BAK on the ocular surface. As it turns out, there is. Vance Thompson and his team have created a new company around the concept of removing BAK from an eye drop on its was out of the bottle. TearClear employs a super-duper secret filter that selectively traps the BAK molecules before the drop reaches the tip of the bottle. Theoretically, any medication that does not employ BAK to traverse the ocular surface can be dispensed from a TearClear bottle. My bet is that TearClear is the transformative product of OIS/AAO 2019.

PAGE BREAK

Unless we are at the beginning of the end of the eye drop age.

When you think about it, eye drops have been the preferred way to get medicine onto and into the eye for centuries. Cleopatra was said to put atropine in her eyes; large pupils have been shown to enhance attractiveness. (As an aside, maybe her induced presbyopia was the reason hieroglyphics are so big.) While we can disagree on the magnitude of the problems, it is clear that a significant percentage of our patients are more effective at lubricating their cheekbones than they are at medicating their eyes. Heck, there are studies that show anywhere from 25% to 50% of bottles end up contaminated. Each eye drop contains anywhere from 35 µl to 45 µL of fluid, likely dousing the ocular surface with more drug than it can absorb in addition to a bunch of BAK.

Four companies went big at AAO on a “no eye drops” approach to treating eye diseases such as dry eye, two of which presented at OIS. Eyenovia calls its technology “piezo print.” From what I saw at OIS, a fine mist is gently sprayed onto the cornea. The Optejet dispenser delivers 8 µL of drug, most likely in non-preserved form. Kedalion AcuStream similarly delivers approximately 10 µL of drug in a thin stream of fluid that makes contact with the cornea before one can blink. They, too, anticipate using preservative-free medicines.

One can readily see obvious applications for both of these systems. In the office, your techs can apply dilating “drops” much more efficiently and effectively, likely saving you money in the process. Elderly and infirm patients are also super candidates for an automated system that is accurate and easy to use. A phone app could track adherence. How about all of the parents whose sanity you have saved, and children saved from the psychological trauma of getting drops from those same parents? Think micro-dose atropine for myopia progression mitigation on the young side, and glaucoma treatment on the old. I see no reason why these would not work; their success in the real world will likely depend entirely on cost.

Another alternative to eye drops is to remove the entire treatment process from the hands of the patient. I have made no secret of my enthusiasm about the drug-eluting punctal plugs developed by Ocular Therapeutix. Sydney Tyson, MD, is an early advocate for moving toward a dropless cataract experience for our patients. He was a driving force behind Dextenza, which delivers non-antimicrobial preserved dexamethasone in a slow-release fashion in the perioperative period. To be honest, this is probably the least interesting application for a drug-eluting plug for DED docs. Dry eye steroids, immunomodulators, antihistamines, you name it — as long as you place the plug properly, you have 100% adherence to treatment. Side effects or complications? Just remove the plug.

PAGE BREAK

Of course, the truly outside-the-box thinkers are not only doing away with drops, they are not even putting medicine on the eye. It should come as no surprise that Michael Ackerman of TrueTear (Allergan) fame has launched a company that seeks to treat DED with a medicine that is applied to the trigeminal nerve in the nose. OC-01 is a preservative-free nasal spray that contains a receptor agonist that activates the parasympathetic trigeminal fibers. Once activated, these nerves stimulate the production of tears from the entire lacrimal functional unit (lacrimal glands, meibomian glands, goblet cells). The ultimate ocular surface treatment may not only do away with drops, it may not even be applied to the ocular surface.

Is the age of eye drops over? Hardly. However, OIS and the AAO meeting introduced us to several alternatives that may allow us to reduce the burden of preservatives on the ocular surface while potentially improving adherence to therapy. It is highly likely that all of the examples above will find their way into our practices.

(I do not have a relationship with any of the companies mentioned above. Weird, huh?)

Disclosure: White reports he is a consultant to Allergan, Shire, Sun, Kala, Ocular Science, Rendia, TearLab, Eyevance and Omeros; is a speaker for Shire, Allergan, Omeros and Sun; and has an ownership interest in Ocular Science and Eyevance.