Findings from the PAGODA and PAVILLION trials for the Port Delivery System with ranibizumab were recently published. Both trials supported the Port Delivery System as a long-acting alternative to frequent intravitreal injections in diabetic eye disease.

PAGODA

The randomized, visual assessor–masked phase III PAGODA clinical trial evaluated the efficacy and safety of continuous ranibizumab 100 mg/mL via Port Delivery System (PDS) with semiannual refill-exchanges over a 64-week period, according to the article recently published in JAMA Ophthalmology. The researchers found that the PDS with ranibizumab administered every 24 weeks was noninferior to monthly intravitreal ranibizumab injections for the treatment of diabetic macular edema (DME).

The researchers enrolled 634 participants across 87 U.S. sites between September 2019 and June 2021. The participants were randomly assigned 3:2 to receive four monthly doses of ranibizumab, 0.5 mg, followed by ranibizumab 100 mg/mL via PDS every 24 weeks (n = 381); or intravitreal ranibizumab, 0.5 mg, every 4 weeks (n = 253). The participants’ mean age was 60.7 years, and 42.7% were female. The study population included 14.7% Black participants, 18.8% Hispanic participants, and 77.1% White participants.

The primary endpoint was the change in best-corrected visual acuity (BCVA) from baseline, averaged over weeks 60 and 64. The adjusted mean BCVA improvement was 9.6 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the PDS group vs 9.4 letters in the monthly injection group (difference = 0.2 letters, 95% confidence interval [CI] = –1.2 to 1.6), which met the noninferiority margin of –4.5 letters.

Central subfield thickness (CST) reductions were also comparable. Participants in the PDS group had a mean decrease of –203.5 μm (95% CI = –212.2 to –194.8), and participants in the monthly group had a mean decrease of –199.7 μm (95% CI = –17.2 to 9.6; difference = –3.8 μm, 95% CI = –17.2 to 9.6). Most participants (95.9%) who received PDS did not require supplemental intravitreal treatment during refill intervals.

An improvement of at least two steps on the Diabetic Retinopathy Severity Scale (DRSS) at week 64 occurred in 39% of the patients who received PDS vs 41.9% in the monthly injection group (difference = –2.9%, 95% CI = –10.7% to 4.9%). While this result didn't meet the prespecified noninferiority margin in the full efficacy population, the modified intent-to-treat analysis showed equivalent improvements (41.6% in both groups).

Adverse events of special interest (AESI) were more common in the PDS group, occurring in 27.5% of participants vs 8.9% of those in the monthly group. However, there were no reported cases of endophthalmitis or retinal detachment in the PDS group. Most AESIs in the PDS group were mild or moderate and resolved by the end of the study. Serious AESIs in the PDS group included conjunctival erosion (1.6%), bleb formation (1.3%), and one case of implant dislocation. Vitreous hemorrhage was reported in 9.7% of PDS patients vs 1.6% in the monthly group. Most events were nonserious and resolved without intervention.

“There was a transient expected postoperative vision drop after PDS implantation, which recovered within 16 weeks,” noted lead study author Arshad Khanani, MD, of the Sierra Eye Associates, and colleagues. “This phenomenon, also observed in the [neovascular age-related macular degeneration] trials, may be driven by media changes in the anterior vitreous and conjunctival sutures, causing tear film interruptions and ocular discomfort. Notably, corresponding mean CST values do not show an increase, which rules out worsening DME as the reason for the vision loss,” they added.

The PDS with ranibizumab 100 mg/mL was approved by the U.S. Food and Drug Administration for DME in February 2025. The approval followed updates to the implant and refill needle, as well as the lifting of a voluntary recall in April 2024 that was initiated in October 2022 as a result of performance issues in earlier versions of the implant.

“The PDS has potential to shift the treatment paradigm for diabetic retinal diseases as the first modality providing continuous anti-VEGF delivery and, therefore, may lead to clinical practice outcomes that are equivalent to clinical trial results in DME. Observational data analyses involving patients with DME treated with PDS will inform the transferability of these results and the benefits of PDS in patients with DME being cared for in clinical practice,” the study authors concluded.

PAVILLION

In the phase III PAVILLION randomized clinical trial, researchers found that the PDS with ranibizumab, administered every 36 weeks, led to significant improvements in diabetic retinopathy severity and reduced disease progression in patients with moderately severe to severe nonproliferative diabetic retinopathy (NPDR) without center-involved DME (CI-DME), according to the recent JAMA Ophthalmology article.

The researchers enrolled 174 participants at 50 U.S. sites. Patients were randomly assigned 5:3 to receive either the PDS filled with ranibizumab 100 mg/mL with refill-exchange every 36 weeks (Q36W) or to a control group with no PDS. Both groups underwent monthly clinical monitoring and were eligible for intravitreal ranibizumab if CI-DME, proliferative diabetic retinopathy (PDR), or anterior segment neovascularization (ASNV) developed.

At week 52, 80.1% of patients in the PDS Q36W group achieved at least a two-step improvement from baseline in the ETDRS-DRSS, compared with only 9% in the control group (difference = 71.1%, 95% CI = 61.0%–81.2%, P < .001).

The rate at which participants developed CI-DME, PDR, or ASNV was significantly lower in the PDS group (7.1%) compared with in the control group (47%) through week 52 (hazard ratio = 0.12, 95% CI = 0.05–0.28, P < .001).

BCVA improved by a mean of 1.4 ETDRS letters in the PDS group compared with a decline of –2.6 letters in the control group (difference = 4 letters, 95% CI = 0.9–7.1, P = .01). CST improved by –18.8 µm in the PDS group vs 2.5 µm in controls (difference = –21.3 µm, 95% CI = –31.7 to –10.9 µm, P < .001).

No patients who received PDS required supplemental treatment during this study, whereas 39.7% of control patients received a mean of 2.9 injections.

Among the 105 PDS-treated participants, ocular AESIs included cataract (6.7%); vitreous hemorrhage (5.7%); conjunctival bleb, conjunctival retraction, and hyphema (each 1.9%); and conjunctival erosion and retinal detachment (each 1%)

All vitreous hemorrhage events occurred within 28 days of PDS implantation, and one case required vitrectomy. No cases of endophthalmitis, implant dislocation, or retinal occlusive vasculitis were reported.

PAVILLION built upon earlier findings from the PANORAMA and DRCR Retina Network Protocol W trials, which demonstrated the benefit of frequent intravitreal anti-VEGF injections in similar patient populations. The PDS system could offer a potential alternative that reduces the treatment burden by delivering continuous intraocular ranibizumab with fewer interventions.

All patients in the PDS group received one refill at approximately 9 months postimplantation. At week 52, 93.4% of the patients in this group remained in the study. Notably, 41.4% of participants self-identified as Hispanic or Latino.

“These potential benefits should be balanced with the transient, postoperative decrease in BCVA from 4 to 12 weeks after implantation and AEs through 52 weeks,” wrote lead study author Dante J. Pieramici, MD, of the California Retina Consultants in Santa Barbara, and colleagues. “Longer-term studies are required to evaluate the safety and efficacy of the PDS as a treatment option vs intravitreal injections for patients with NPDR without CI-DME, which may help inform optimal management strategies for the PDS in clinical practice,” they concluded.

Disclosure information can be found in the published studies.