Improvements in drug delivery

New drugs and slow-release devices could improve compliance, reduce side-effects

Leigh Spielberg

Posted: Friday, February 1, 2019

Antonio Fea MD, PhD

A new generation of drugs and delivery systems should help improve compliance and reduce side-effects associated with conventional glaucoma treatments, said Antonio Fea MD, PhD, at the 36th Congress of the ESCRS in Vienna.

With recent studies indicating that only 30% of glaucoma patients had refilled their initial medication three years after the first dispensing, the time has come for new approaches, said Dr Fea, Turin University Eye Clinic, Italy.

One approach is to develop agents that do a better job of lowering intraocular pressure, he noted. For example, Vyzulta (latonoprostene bunod 0.024% solution), which is commercially available in the USA but not yet in Europe, is a prostaglandin analogue that releases nitric oxide. It acts via the uveoscleral pathway and induces relaxation of the trabecular meshwork.

In the VOYAGER study, Vyzulta demonstrated statistically significant greater mean IOP reduction compared with Xalatan 0.005% at day 28, with a similar safety profile and only 1% discontinuation.

“However, the ultimate goal is to develop drugs with alternate mechanisms and low systemic side-effects. After all, up to 50% of an eye drop is lost immediately upon instillation, and less than 5% reaches the aqueous humour,” he said.

Therefore, a primary focus of research has been into other treatment modalities that cover the area between topical application and surgical intervention.

Dr Fea outlined newer treatments that may reduce dependence on topical drops. Research into long-term release of drugs is very active, he said. Anatomical locations for depot implants include the ocular surface (contact lenses), the fornices (periocular inserts), the upper or lower punctum and canaliculi (plugs and inserts), the subconjunctival space (depots), the anterior chamber and supraciliary space (reservoirs) and even the posterior segment.

Contact lenses can be imprinted with medication or infused with nanoparticles. Subconjunctivally injected reservoirs of latanoprost and bimatoprost liposomes are in phase I studies and suggest that scleral penetration of drugs is better than corneal, said Dr Fea.

The iDose, from Glaukos Corporation in California, is a titanium drug reservoir anchored in the trabecular meshwork that elutes bimatoprost for a period of up to six months. In a US Phase II trial of 154 patients, there were no reports of hyperaemia, the most common problem with prostaglandin analogues, he reported.

“Which method will gain acceptance will depend on a combination of medical concerns such as safety, efficacy and side-effects, as well as logistical concerns like availability, cost and reimbursement,” he concluded.

Antonio Maria Fea:

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