medwireNews: Continuous ranibizumab treatment given every 6 months via the Port Delivery System (PDS) to patients with diabetic macular edema (DME) results in comparable visual gains as when it is given monthly by intravitreal injection, suggest findings from the Pagoda trial.
The trial was published in JAMA Ophthalmology alongside findings from the Pavilion trial, which showed that patients with nonproliferative diabetic retinopathy without DME were more likely to improve by at least two levels on the Diabetic Retinopathy Severity Scale (DRSS) at 52 weeks with ranibizumab treatment every 36 weeks via the PDS than with monitoring alone.
The PDS is a surgically inserted, refillable scleral implant that allows continuous drug delivery to the vitreous cavity.
Reflecting on both findings in a related commentary, Adam Glassman (Jaeb Center for Health Research, Tampa, Florida, USA) says that “[t]he PDS is an innovative treatment in the landscape of diabetic eye disease treatment, with the potential to reduce treatment burden and improve patient treatment adherence making it an appealing option for some patients.”
However, he notes that “balancing its potential benefits against its drawbacks and unknowns will be key to integrating into clinical practice.”
For the Pagoda trial, 634 treatment-naïve patients (57.3% men) with center-involved DME and a mean age of 60.7 years were randomly assigned to receive the anti-vascular endothelial growth factor (VEGF) ranibizumab via PDS or as a monthly 0.5-mg injection. The PDS group received intravitreal ranibizumab 0.5 mg every 4 weeks for the first 3 months followed by implantation of the prefilled PDS at week 16 that continuously delivered ranibizumab 100 mg/mL with a refill every 24 weeks.
The change in best-corrected visual acuity (BCVA), averaged over weeks 60 and 64, increased in the patients receiving PDS by a mean of 9.6 letters, from 65 letters at baseline, compared with 9.4 letters among those receiving monthly injections. The nonsignificant difference of 0.2 letters between the groups demonstrated the noninferiority of PDS.
Study authors Arshad Khanani (University of Nevada, Reno, USA) and colleagues note that patients in the PDS group had a “transient expected postoperative vision drop after PDS implantation,” of 6.7 letters, on average, but this had recovered to levels comparable with monthly ranibizumab within 16 weeks.
In terms of safety, the PDS group were more likely to experience adverse events (AEs) of special interest than the monthly injection group by week 64 (27.5 vs 8.9%). In all, there were 12 serious AEs of special interest in the PDS group – five conjunctival erosions, four conjunctival blebs, and one each of cataract, conjunctival retraction, vitreous hemorrhage, and implant dislocation. There were just two in the monthly injection group, one each of cataract and endophthalmitis.
The researchers highlight that there were no cases of endophthalmitis or retinal detachment in the PDS group.
“Data from Pagoda formed the basis for seeking FDA approval for the DME indication, which was granted in February 2025,” say Khanani et al.
They believe that “use of the PDS may translate into reduced clinic appointments and lower disruption to patients’ work and social lives, with potential positive effects on quality of life for patients and their families.”
The Pavilion trial involved 174 adults with moderately severe or severe nonproliferative diabetic retinopathy, who scored 47 or 53 points on the DRSS at baseline, respectively. They had a mean age of 54 years and 57.5% were men.
Of these patients, 106 were randomly assigned to receive ranibizumab 100 mg/mL via the PDS, which involved two 0.5 mg doses of intravitreal ranibizumab injected on day 1 and week 4, followed by implantation of the PDS within 14 days, which was then refilled every 36 weeks.
At week 52, 80.1% of patients receiving ranibizumab via PDS had improved by two steps on the DRSS, which was a significant 71.1% more than the 9.0% of control patients (n=68) who underwent study visits every 4 weeks for monitoring and clinical observation without PDS. The mean change in BCVA at this timepoint was an increase of 1.4 letters for the PDS group and a decrease of 2.6 letters for the control group, a significant difference.
As in the Pagoda study, the patients in the PDS group experienced a transient, surgery-related decrease in BCVA of 7.4 letters at 4 weeks after implantation, but this “resolved approximately 12 weeks after implantation, and mean BCVA was maintained thereafter,” note the investigators.
Ranibizumab via PDS was also superior to placebo for secondary outcomes, including a significantly lower rate of center-involved DME, proliferative diabetic retinopathy, and anterior segment neovascularization (7.1 vs 47.0%).
Safety outcomes were only summarized for the PDS group, 16.2% of whom had a total of 271 ocular AEs of special interest. These included cataracts in 6.7% of patients, vitreous hemorrhage in 5.7%, conjunctival bleb, conjunctival retraction, and hyphema each in 1.9% of patients, and conjunctival erosion and retinal detachment each in 1.0% of patients.
Dante Pieramici (California Retina Consultants, Santa Barbara, USA) and fellow Pavilion investigators say that “the PDS offers a unique strategy for continuous VEGF inhibition that can maintain vision and reduce disease progression with infrequent treatment administration.”
They conclude: “This approach may help prevent vision-threatening complications by providing sustained anti-VEGF therapy, particularly in cases where lapses in care or delayed monitoring might otherwise lead to substantial vision loss before treatment is initiated.”
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JAMA Ophthalmol 2025; doi:10.1001/jamaophthalmol.2025.0001
JAMA Ophthalmol 2025; doi:10.1001/jamaophthalmol.2025.0006
JAMA Ophthalmol 2025; doi:10.1001/jamaophthalmol.2025.0007