麻豆传媒

SAN ANTONIO -- An ocular implant that provided 6 months of continuous-release anti-VEGF therapy achieved vision and anatomic outcomes equivalent to standard monthly intravitreal injections for neovascular age-related macular degeneration (AMD), according to updated results of a randomized trial.

After 40 weeks of follow-up, patients randomized to the port delivery system (PDS) had a mean increase of 0.2 ETDRS letters from baseline as compared with 0.5 for monthly ranibizumab (Lucentis). The 0.3-letter difference met criteria for equivalence in best-corrected visual acuity (BCVA). The mean change in central point thickness (CPT, a secondary endpoint) differed by 2.8 μm, also a nonsignificant difference.

Results have been maintained during follow-up to 72 weeks. More than 90% of patients assigned to the PDS did not require supplemental anti-VEGF treatment between scheduled refills. With 79 weeks of follow-up for safety, the most notable adverse events (AE) have been three implant dislocations, thought to arise from oversized incisions during initial insertion, and four cases of endophthalmitis, three of which were associated with conjunctival retraction, reported Carl Awh, MD, of Tennessee Retina in Nashville, at the American Society of Retina Specialists (ASRS) meeting.

"PDS met its primary endpoint for the treatment of neovascular AMD, and these vision and anatomic results were maintained up to 72 weeks with every-6-months refills in the PDS group," said Awh at the ASRS "Wet AMD 2 Symposium."

"Supplemental treatment seems to be rare. Like with all surgical procedures, our continued experience has led to modifications that may decrease the risk of adverse events, particularly meticulous attention to the conjunctiva," he stated.

The FDA is expected to make a decision about approval of the PDS before the end of October, Awh added.

The findings came from the phase III trial, which compared the PDS with standard intravitreal injections of ranibizumab in 415 patients (randomized 3:2) with previously treated neovascular AMD. Patients had received an average of five anti-VEGF injections at enrollment.

The refillable PDS implant holds 100 mg/mL of ranibizumab, which is released continually and designed for refill at 6-month intervals. Patients assigned to standard treatment with ranibizumab received intravitreal injections every 4 weeks. Need for supplemental treatment was determined from a combination of changes in vision and central subfield thickness attributable to AMD.

The primary endpoint was BCVA at 40 weeks, and the trial met that endpoint, as .

"We found no significant change in either arm," said Awh. "Because patients had received a mean of five injections prior to their first study visit, the stability was excellent and was the desired endpoint... . Over the next 36 weeks, three patients treated with PDS maintained equivalent vision to those receiving monthly ranibizumab injections. We saw the same effect with anatomy, so central OCT thickness had excellent response in the PDS and ranibizumab arms at 36 and 40 weeks and this was maintained out to 72 weeks."

AE rates appeared to decline with PDS versus ranibizumab after 40 weeks. The implant dislocations were unanticipated and resulted from a longer-than-recommended incision in the sclera at the time of implantation, said Awh.

The four cases of endophthalmitis all involved circumstances that could have contributed to the inflammation. In one case, one male patient, age 68, had concurrent conjunctival retraction and reported the he had cleaned a septic tank prior to developing endophthalmitis. The PDS implant tested positive for E. faecalis. A second case involved a patient with a history of autoimmune disease and intraocular inflammation. The remaining two cases were associated with conjunctival retraction, and the implant tested positive for S. aureus in one of the cases.

During a post-presentation discussion, an audience member asked Awh about indications for repairing conjunctival retraction.

"We've learned a lot during the experience," said Awh. "Some things we might ignore with a post-[scleral] buckle patient -- where you see a little bit of exposure that can be tolerated for a long time -- you really can't wait with the PDS. The minute you see the conjunctiva behaving abnormally, it's probably reasonable to think about revising it."

"Among patients who've had endophthalmitis, it fairly consistently involved some issue with the exposure of the device," he added. "I think that just covering that fairly early and then, most importantly, doing things at the initial implantation that prevent that from happening, are going to be critical."

In response to another question, Awh said he would initially consider the PDS for his "frequent fliers," patients who require intravitreal injections every 4 to 6 weeks and want a different treatment option. As experience with the device increases, the indications might expand.

Awh also put in a plug for Genentech's training program for PDS implantation and management "because things can happen that can be directly related to your surgical procedure and your technique."

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