May 2019


Technology & Innovation
Innovations in drug delivery

by Liz Hillman EyeWorld Senior Staff Writer

Allergan is working on a bimatoprost periocular ring, as seen in the lower right quadrant of this eye.
Source: John Sheppard, MD

“Drops as we know them will cease to exist over the next couple of years as new drug delivery systems change the way we deliver medications.”
—Eric Donnenfeld, MD

Dr. Donnenfeld injects Dexycu after cataract surgery.
Source: Eric Donnenfeld, MD


Activity and innovation in the drug delivery space—whether improving drops or developing external implants or intraocular options—is booming.
“There are significant unmet needs in drug delivery, and our ability to resolve those needs will result in better patient care,” said Eric Donnenfeld, MD. He calls these areas the “5 Cs” of drug delivery: (1) compliance, (2) corneal problems (dry eye), (3) comfort, (4) cost, and (5) cosmesis (red eyes). “The major unmet need is certainly compliance,” he said.
So what are the solutions?


One way to improve drop compliance burden is to combine multiple drops and/or use alternative concentrations, said Russel Swan, MD, admitting that the U.S. market lags behind other countries on this front for commercially available options. There are some options, however, available through compounding pharmacies.
Vehicles that help medical agents stay on the surface of the eye longer are also coming of age. Dr. Donnenfeld mentioned DuraSite (InSite Vision), which uses a muco-adhesive that stays in the tear film. This technology is currently used by AzaSite (azithromycin, Akorn Pharmaceuticals), Besivance (besifloxacin, Bausch + Lomb), and BromSite (bromfenac, Sun Ophthalmics). Another innovation in drops, Dr. Donnenfeld said, is the use of nanotechnology to increase penetration of medication inside
the eye. Products with such technology include Inveltys (loteprednol, Kala Pharmaceuticals) and Lotemax SM (loteprednol, Bausch + Lomb). Inveltys has a mucus-penetrating particle to allow for only twice daily dosage for inflammation and pain after ocular surgery, while Lotemax SM (also for inflammation and pain) has a submicron formulation that dissolves quickly into the eye before tear washout.
There have been advances in the bottles to deliver the drops properly, but the use of bottles with target systems is not widespread, Dr. Donnenfeld said. TearClear is making a filter that removes preservatives that can be toxic to the ocular surface (namely benzalkonium chloride) from the drop as it exits the bottle, while keeping the solution inside preserved.

External implants

External inserts have significant advantages, Dr. Donnenfeld said, because they can be applied once and provide sustained release of a medication over a period of time. Dextenza (Ocular Therapeutix), for example, is an FDA-approved bioabsorbable, intracanalicular, hydrogel plug that provides sustained release of a consistent amount of dexamethasone for 1 month after cataract surgery. According to Cynthia Matossian, MD, Dextenza is currently indicated for pain, but Ocular Therapeutix submitted a New Drug Application to the FDA to receive an indication for inflammation and it is working on obtaining a J code and pass-through designation as well.
Mati Therapeutics is developing a different punctal plug for drug delivery. Dr. Donnenfeld said it just finished Phase 2 trials, of which he was the primary author/investigator, for a nonsteroidal medication for 3 months. But, Dr. Donnenfeld added, almost any medication could be used here.
“I think that the best application for this type of punctal plug is dry eye. Not only do you get the advantage of the punctal plug, which helps dry eye, but you also get the advantage of sustained release agents,” Dr. Donnenfeld said, noting its value for glaucoma and cataract surgery as well.
Another insert is a bimatoprost periocular ring (Allergan), which is under investigation to provide at least 4 months of glaucoma therapy. Finally, Dr. Donnenfeld mentioned the Topical Ophthalmic Drug Delivery Device (TODDD), an under the eyelid device being developed by Vista Scientific, currently focused on sustained timolol delivery.

Intraocular options

We are now in an era where there is a means of reducing compliance issues by delivering drugs right to the target tissue, Dr. Matossian said, specifically noting the FDA approval and official commercial roll-out of Dexycu (dexamethasone, EyePoint Pharmaceuticals). Dexycu has a J code and pass-through status. This injection, Dr. Matossian said, eliminates the most burdensome and confusing post-cataract surgery drops—the steroid—which has to be used several times a day and tapered over several weeks. Dexycu mimics this titration over time, she said.
Dr. Donnenfeld, first author on the clinical trials for Dexycu, said studies showed it was identical in reducing cell and flare compared to Pred Forte (prednisolone, Allergan), and IOP was not a significant issue.
“It looks to have safety and efficacy and eliminates the drop burden,” he said. Plus, there will be no cost to the patient, no cost to the surgery center, and no cost to the doctor. “I think this will be widely appreciated by the patient to not have to pay for a medication and to reduce the compliance issues.”
FDA approval of this product, Dr. Donnenfeld said, is a “major step in the right direction for drug delivery overall, and hopefully, all of our medications will be prepared like this in the near future.”
Dr. Matossian said Dexycu injection should be comfortable to cataract surgeons because they are in the same space, injecting the steroid above the IOL under the iris. She said she will eventually use Dexycu with intracameral antibiotics as well, which will leave her cataract patients with just one NSAID drop a day.
Injection of intracameral antibiotics and compounded medications is a relatively common practice after cataract surgery. Dr. Swan said he injects compounded dexamethasone, moxifloxacin, and ketorolac at the conclusion of cataract surgery.
“I think there is an undeniable decrease of endophthalmitis with intracameral antibiotics,” Dr. Swan said.
On the glaucoma front, Allergan is working on a bimatoprost sustained release, biodegradable, anterior chamber implant, while Glaukos has reported data on iDose, an intraocular implant that has provided sustained IOP reduction over at least 12 months.
“From the standpoint of the glaucoma space, that’s where there is the most excitement. There are a lot of different opportunities there,” Dr. Swan said. “The last 5 to 10 years have been dominated by MIGS,” he added later, “but I think drug delivery will be the next tale to tell, and it will cross over into many other areas of ophthalmology. We will have more options to take compliance out of patients’ hands and improve delivery without ocular surface side effects.”
Overall, Dr. Donnenfeld called drug delivery the “most exciting, disruptive area in ophthalmology today.”
“Drops as we know them will cease to exist over the next couple of years as new drug delivery systems change the way we deliver medications in a more effective and compliant manner for patients,” he said.
Dr. Matossian expressed a similar sentiment and added that the minimization of drops dovetails with the premium cataract surgery experience that many patients have come to expect.
“Patients’ expectation is that their cataract surgery is going to have a positive impact
on their life, and decreasing the drop burden will reinforce that positive patient journey,” she said.

At a glance

• Innovation in drug delivery is primarily driven by the need to improve patient compliance and reduce adverse side effects from drops.
• Combinations, nanotechnology, and other vehicles are improving some drop pitfalls.
• External inserts, such as punctal plugs, are offering opportunities for easy insertion and removal and sustained-release medication.
• Intraocular options include intracameral injections of antibiotics and compounded medications, sustained-release solutions, and medication-eluting implants.

Contact information

Swan: russell.swan@vance

About the doctors

Eric Donnenfeld, MD
Ophthalmic Consultants of
Long Island
Garden City, New York

Cynthia Matossian, MD
Matossian Eye Associates
Doylestown, Pennsylvania

Russell Swan, MD
Vance Thompson Vision
Bozeman, Montana

Financial interest

: Allergan, EyePoint Pharmaceuticals, Alcon, Bausch + Lomb, Kala Pharmaceuticals, Ocular Therapeutix, Mati Therapeutics
Matossian: Ocular Therapeutix, EyePoint Pharmaceuticals
Swan: Alcon, Glaukos, Allergan

Dr. Donnenfeld's 5 Cs drug delivery

1. Compliance
2. Corneal problems (dry eye)
3. Comfort
4. Cost
5. Cosmesis (red eyes)

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