Implant Matches Topical Timolol for Intraocular Pressure Control, With Good Safety

SAN DIEGO -- A drug-eluting intraocular implant proved noninferior to daily topical timolol for treating intraocular pressure (IOP), according to data from two randomized trials.

From a mean baseline of 24 mm Hg, the travoprost intraocular implant (TII) reduced IOP by 6.6-8.5 mm Hg during the first 3 months of treatment in the GC-010 trial, and by 6.7-8.4 mm Hg in the GC-012 trial. Respective values for timolol were 6.6-7.7 mm Hg and 6.8-7.2 mm Hg.

At 12 months, more than 90% of patients treated with the TII had well-controlled IOP with the same or less IOP-lowering medication as compared with 67% of patients randomized to timolol. Additionally, investigators found that the device can be exchanged with no evidence of clinically significant endothelial cell loss after the exchange, reported John Berdahl, MD, of Vance Thompson Vision in Sioux Falls, South Dakota, during the American Society of Cataract and Refractive Surgery annual meeting.

"The travoprost implant did achieve noninferiority to timolol, and 81% of patients were [IOP-lowering] medication free after 12 months," said Berdahl. "It has a favorable safety profile, with low rates of conjunctival hyperemia, no corneal endothelial cell loss, no serious corneal adverse events, and no adverse events of periorbital fat atrophy. It looks like it can be safely removed and replaced."

In response to a question following the presentation, Berdahl said he is unaware of any implants that have became dislodged or otherwise fallen out of place.

Managing IOP remains the only treatable risk factor for glaucoma, which is expected to affect 95 million people worldwide by 2030. Topical treatments represent standard first-line treatment for open-angle glaucoma (OAG), which accounts for about 80% of all glaucoma, Berdahl noted.

Medication adherence poses a major obstacle to effective treatment with topical therapies, and 40-60% of patients with newly prescribed medication discontinue treatment within a year, Berdahl said. An estimated 90% of patients with glaucoma are noncompliant with their medication.

The TII was designed with the goal of providing effective IOP lowering while avoiding the challenges of topical therapy. A capsule containing a novel formulation of the prostaglandin analog travoprost is inserted by means of a micro-invasive intracameral procedure. The device continually releases the medication over time.

Berdahl reported findings from two phase III randomized trials comparing the TII with conventional topical timolol. The primary outcomes were noninferiority to timolol at 3 months with respect to IOP reduction and safety outcomes. Eligible patients were adults with a diagnosis of OAG or ocular hypertension currently managed with as many as two medications.

The two trials involved a total of 1,150 patients, enrolled at 89 sites. Patients were randomized 1:1 to the TII or sham procedure/timolol 0.5% twice daily. The primary efficacy outcome was reduction in IOP from baseline to 3 months. The primary safety outcome comprised complications, adverse events (AEs), and secondary surgeries at 12 months.

The mean baseline IOP ranged from 24.02 to 24.32 mm Hg. The results showed a numerical trend in favor of the TII, satisfying the statistical criteria for noninferiority. In GC-010, the AEs most often associated with the TII were iritis (6.2%), reduction in visual acuity and increased IOP (4.6% each), and dry eye and cataract (3.6% each). In GC-012, the most common TII-associated AEs were iritis and IOP elevation (5.5% each), eye pain (4.4%), and nervous system disorders (3.8%).

Berdahl also reported findings from a small prospective multicenter study of device exchange. Data analysis included 33 patients who received the TII during a phase II trial and subsequently underwent device exchange. All patients had at least 12 months follow-up after the exchange, and some patients were followed beyond 5 years (including from the time of the original procedure in the phase II study).

No patient had clinically meaningful endothelial cell loss (≥30%) during the evaluation period, said Berdahl.

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