Medical treatment of glaucoma is evolving to include internal and external drug delivery systems that will ensure patient compliance for long periods.
Internal delivery systems
In light of this, Dr. Baudouin and his team are involved in developing periocular or intraocular longterm delivery systems. While this is not a revolutionary new approach, the development of ganciclovir (Vitrasert, Auritec Pharmaceuticals), an implant to treat cytomegalovirus retinitis, and then the introduction of the dexamethasone intravitreal implant (Ozurdex, Allergan) and fluocinolone acetonide intravitreal implant (Iluvien, Alimera Sciences) were major steps within this technology because of the slow release and duration of biodegradable drug delivery, respectively, that they provided.
More recently, Allergan developed an intracameral implant loaded with brimatoprost.
In an ongoing phase I/II study, the six-month results showed, according to Dr. Baudouin, that the loading dose worked quite well; the IOP reduction was slightly less than that achieved with a topical anti-glaucoma medication, but the patients were fully compliant, which is not the case in real life. He emphasized that at six months, 71% of patients implanted with the device did not require rescue medication.
Regarding safety, no more side effects occurred with the implants compared with the topical medication if excluding the few transient side effects related to the procedure itself; 78% of patients indicated that they would undergo the procedure again.
Other intracameral implants include one containing latanoprost (PolyActiva) and one with travoprost XR (Envisia Therapeutics), both provided similar results to those of brimatoprost.
Glaukos developed the iDose Travoprost, a non-degradable device implanted into the trabecular meshwork that should deliver the drug for a minimum of 1 year; the results are good compared to timolol with no side effects but the technique requires replacing the device after one year, according to Dr. Baudouin.
External delivery systems
Conjunctival rings containing brimatoprost, the Helios (ForSight Vision5) BIM ring, delivers the drug for six months after insertion in the fornix; a phase II study demonstrated that the device did not achieve noninferiority to timolol.
Because of the nature of such study where one eye received the ring, patient compliance was naturally much higher for instilling timolol in the fellow eye.
However, the safety profile was wanting: 28 dislodgements occurred in 15 patients and nine patients withdrew from the study because of the side effects compared with only one receiving timolol.
The long-term results after readministration were stable, although the IOP was slightly higher compared with timolol.
Travoprost is contained in two new delivery systems, TODDD (Amorphex Therapeutics) is a polymer implanted subtarsally in the superior lid intended to deliver drug for 180 days, and OTX-TP (Ocular Therapeutix) is a punctal plug that delivers drug for 90 days. A phase IIb study of the latter device showed a greater IOP decrease at 90 days with timolol that likely resulted from punctal occlusion.