Eyeworld

EW GLAUCOMA 28 May 2018 Pharmaceutical focus by Maxine Lipner EyeWorld Senior Contributing Writer Gary Novack, PhD, president of PharmaLogic Development, San Rafael, California, and visiting pro- fessor of pharmacology and oph- thalmology, University of California Davis School of Medicine, cited the pilocarpine-filled Ocusert as an early iteration of these sustained-release devices. There can be pros and cons to these, Dr. Novack stressed. "Ocusert, developed in the 1970s, did a great job of delivering pilo- carpine to the tear film for 1 week, but unfortunately could slide across the cornea to block the vision," Dr. Novack said. Dr. Mansberger said that any location in the eye is possible for sustained delivery. In his view, the punctal plugs show some promise. "You can see that they're there," Dr. Mansberger said, adding that these are slowly eluting medicine. The question is whether patients will be amenable to putting in such a plug and stretching the puncta, as well as whether there are any long-term side effects. "I think that patients would look at this favorably because they don't like taking drops every day," Dr. Novack said, adding, however, that it's hard to know which of the sustained-release approaches patients would prefer. There can also be unintended consequences. "By doing one thing, you perturb the system in another way," he said. In considering what molecules might be most likely to succeed in a sustained delivery approach, Dr. No- vack stressed that this depends on the type of delivery system. "If it's a 'zero order,' i.e., constant delivery with respect to time system, a mol- ecule like brimonidine or timolol is most appropriate," he said. "If it's a pulsatile, i.e., peaks and troughs system, a molecule like the prosta- glandins is the better choice." The fact that the prostaglandins tend to do better with such pulsatile de- livery is supported by the data that indicate that twice-a-day dosing of this drug is less effective than once- a-day dosing. For molecules such as pilocarpine, timolol, and brimoni- dine that have variable durations of activity, constant delivery seems to be a workable solution, Dr. Novack said. said. "The external group includes delivery emulsions, fornix-based rings, contact lenses, subconjuncti- val injections, and punctal plugs." The internal group are placed in the anterior chamber and include bio- degradable implants or a replaceable device put on an intraocular lens or a MIGS device. Examples in- clude the iDose Travoprost implant (Glaukos, San Clemente, California) and Bimatoprost Sustained Release (Allergan, Dublin, Ireland). Devices placed internally would need to have higher efficacy, Dr. Bacharach pointed out. "With eGAP you might give up some efficacy because of perceived benefits on the safety side," he said. "If you place a pharmaceutical product inside the eye, one benefit would be allowing for a lower concentration or reduced amount of medicine as it is closer to the targeted tissue." An example of a replaceable eGAP would be the bimatoprost sus- tained-release ring (Allergan), which is a flexible ring placed in the fornix and barely visible, Dr. Bacharach said. An example of the iGAP would be the iDose. "The iDose provides sustained IOP reduction over time via a delivery cartridge of propri- etary travoprost oil that has demon- strated robust IOP reduction over months," he said. Once the agent is delivered, the practitioner can remove the canister through a small microincision in the cornea and replace this through the incision. Bimatoprost sustained-release is a dissolvable pellet that would not need to be removed, he noted, adding that the physician would need to put in a new one once it was gone. Dr. Mansberger pointed out that there can be issues with some of the sustained-release approaches. The bimatoprost ring, for example, has had some efficacy issues, he noted. "It didn't have as much IOP-lower- ing as timolol," Dr. Mansberger said. "Also, there is a foreign body in the fornix of the eye, which can create all the issues that you might get from a contact lens-type process." This approach is similar to one used in the past in which a silicone sack filled with pilocarpine was placed in the lower fornix where it would remain for a period of time. "I think that it's a great oppor- tunity," he said, adding that using this approach in glaucoma would teach practitioners about the impact of such devices in the angle and how the eye tolerates having some- thing small in the anterior chamber over time. Steven Mansberger, MD, vice chair and director of glaucoma ser- vices, Legacy Devers Eye Institute, Portland, Oregon, pointed out that any MIGS devices that use the out- flow tract collector system are going to require medicines. In his view, sustained delivery implants will fill an important void. "We don't have a sustained delivery device available right now, so there's a need for this type of treatment for those patients who can't remember to use their eye drops every day," he said. While not all would likely want this, sustained delivery represents a way for many of these patients to be treated for a long period without much effort on their part. Considering the possibilities There are a variety of possible ap- proaches for sustained delivery, Dr. Bacharach said. He refers to these as GAP (guided administration of pharmaceuticals) therapy and breaks them into two groups, eGAP and iGAP. "The eGAP is external deliv- ery, and the iGAP is internal," he New delivery possibilities for glaucoma F or glaucoma patients, using eye drops is often a daily ritual. The holy grail would be an implant that could deliver the needed medica- tion on cue. From punctal plugs to rings and implants and more, here's the latest in this area. Even in this era with so much attention in glaucoma on MIGS technology, there's ample room for sustained-release devices, according to Jason Bacharach, MD, found- ing partner and medical director, North Bay Eye Associates, Sonoma County, California. He views these as ancillary treatment opportunities. "They're not necessarily separate," he said. "You could deliver a drug through a MIGS-type device that is potentially replaced over time." For example, practitioners could deliver one of the commonly used topical agents or even a novel agent through a MIGS device that would provide ancillary intraocular pressure reduction over what a stent without pharmaceutical products might provide, Dr. Bacharach ex- plained. This is akin to the coated stents being regularly used in the cardiology world, which work better than the stent alone. Examining the sustained front continued on page 30 The bimatoprost sustained-release ring is an example of an external guided administration of pharmaceuticals. Source: Allergan

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