BALANCING RISK

We certainly know we have issues with putting drops in, and remembering to put drops in, and red eyes Ike K Ahmed MD

Several devices that release glaucoma medications for periods ranging from a few hours to one year are close to reality, Ike K Ahmed MD of the University of Toronto, Canada, told Glaucoma Day at the 2013 ASCRS Symposium. They hold potential for targeting IOP-lowering and neuroprotective agents more directly to their sites of action, and reducing poor patient adherence and debilitating side effects often seen with eye drops. “We certainly know we have issues with putting drops in, and remembering to put drops in, and red eyes. These are problems we encounter every day. We ignore them, we try to deal with them, but we’d like to see better alternatives,” Dr Ahmed said. Even with good adherence, persistence of medication at the site of action is often an issue with topical administration, he added. Recent research suggests that patients, too, may prefer alternatives to daily drops, even if it means undergoing periodic subconjunctival injections, and higher costs, Dr Ahmed said. Patients in Singapore who admit non-adherence, who are on more medications or have higher frequency of dosing are more likely to accept alternates (Chong RS et al. J Glaucoma Volume 22, No 3, March 2013).

Balancing performance and risk

Ideally, an extended release system should be relatively easy to use or implant, work long enough to be worth the extra trouble and be effective in reducing intraocular pressure (IOP) and improving diurnal control, Dr Ahmed said. The level of invasiveness and risk profile also should compare favourably to existing therapies. “As clinicians we will have to figure out what exactly will be attractive for our patients.” Devices close to market use a variety of novel delivery concepts to achieve these ends. One improves the performance of eye drops with mucus penetrating particles (Kala Pharmaceuticals). These nanoparticles keep drugs on the ocular surface longer by defeating the mucosal barrier, making them resistant to being washed away by tears, which extends duration of action. Others repurpose previously developed devices. A latanoprost-eluting contact lens (Massachusetts Eye and Ear Infirmary) works for two weeks to a month. Drug-eluting punctual plugs (Ocular Therapeutix), could deliver prostaglandins or corticosteroids for two to three months. Drug-eluting intravitreal depots (Ocular Therapeutix), the Durasert implant (pSividia Corp), implantable collagen wafers and gels injected in the vitreous or anterior chamber extend release from four to six months. A biodegradable implant installed subconjunctivally or intravitreally with a 21-gauge needle may deliver a combination of drugs for three to six months (PolyActivia). The Replenish ophthalmic micropump is attached to the eye and delivers drugs for 12 months. It is recharged wirelessly and can be refilled with a 31-gauge needle for even longer use. Microneedles, injected gels and collagen depots that sit on the ocular surface under the upper eyelid are also in development. “With our current regulatory environment we are probably four or five years away from many of these. But this is very exciting for us and our patients to provide new alternatives for glaucoma drug therapy,” Dr Ahmed concluded.