Clinical Studies:
PAGODA
Citation: Khanani AM, Campochiaro PA, Graff JM, et al. Continuous Ranibizumab via Port Delivery System vs Monthly Ranibizumab for Treatment of Diabetic Macular Edema: The Pagoda Randomized Clinical Trial. JAMA Ophthalmol. 2025;143(4):326-335.
Key Points
- A 24‑week refill regimen of ranibizumab 100 mg/mL delivered via the implanted Port Delivery System (PDS) preserved vision and anatomy as well as monthly 0.5 mg intravitreal ranibizumab injections in patients with diabetic macular edema (DME).
- Adjusted mean best corrected visual acuity (BCVA) gain through week 64: +9.6 ETDRS letters (PDS) vs +9.4 letters (monthly); PDS met the prespecified non‑inferiority margin (–4.5 letters).
- Durability: 95.9% of PDS eyes required no supplemental anti‑VEGF injections during each 24‑week refill interval.
- Treatment burden fell by >55 %: mean of 6 ranibizumab administrations (implant + refills) vs 14 monthly injections through week 64.
- Adverse ocular events of special interest occurred in 27.5% of patients in PDS group compared to 8.9% of patients in the monthly ranibizumab group. Endophthalmitis occurred in 0% of PDS-treated eyes and 0.3% of the monthly ranibizumab-treated eyes. Overall systemic safety matched monthly injections.
-
Objective
To determine whether continuous delivery of ranibizumab via the PDS, refilled every 24 weeks, is non‑inferior to monthly intravitreal ranibizumab 0.5 mg in eyes with center‑involved DME over 64 weeks.
-
Study Design
Phase 3, multicenter, randomized, controlled open-label, visual-acuity assessor-masked non-inferiority trial with 3:2 allocation of PDS to monthly intravitreal ranibizumab. Primary endpoint was mean BCVA change at weeks 60 and 64.
Subjects
- Major Inclusion Criteria:
- Adults ≥18 years with center‑involved DME due to type 1 or type 2 diabetes
- BCVA 78 to 25 (20/32 to 20/320) ETDRS letters
- Subjects were required to be either treatment-naïve in the study eye or to have had no treatment within the prior 6 months
- Major Exclusion Criteria:
- High-risk proliferative diabetic retinopathy (PDR)
- Any history of panretinal photocoagulation (PRP)
- History of macular laser within 6 months of randomization
- Any intravitreal corticosteroid at any time prior to randomization
- Tractional retinal detachment (TRD) or preretinal fibrosis
- Active intraocular infection or inflammation
- Any macular disease that could confound results
Randomization Scheme/Study Interventions
- PDS Q24W (n = 381): Four monthly loading injections of ranibizumab 0.5 mg, followed by surgical implantation of the PDS pre‑filled with ranibizumab 100 mg/mL (implant at week 16, allowed through week 20). In‑clinic refill‑exchange every 24 weeks. Supplemental 0.5 mg intravitreal ranibizumab was permitted per protocol criteria.
- Monthly intravitreal ranibizumab 0.5 mg (n = 253): Intravitreal ranibizumab injections every 4 weeks through week 60.
Results
- Mean BCVA change: +9.6 letters (PDS) vs +9.4 letters (monthly) — non‑inferior
- ≥2‑step Diabetic Retinopathy Severity Score (DRSS) improvement: 39.0% (PDS) vs 41.9 % (monthly) — did not meet non‑inferiority margin but numerically comparable.
- No supplemental injections: 95.9% (refill-exchange interval 1) and 97.4% (refill-exchange interval 2) of assessed PDS eyes.
- Mean study‑eye ranibizumab administrations: 6 (loading intravitreal ranibizumab injections + PDS implant + refills) vs 14 (monthly injections).
- Ocular adverse events of special interest: 27.5% (PDS) vs 8.9% (monthly); vitreous hemorrhage 9.7%, conjunctival bleb/bleb leak 7.8%, endophthalmitis 0% in the PDS arm.
Conclusions
- The PAGODA trial demonstrated that a fixed 6-month refill regimen of PDS-ranibizumab after four intravitreal ranibizumab loading doses sustains visual and anatomic outcomes equivalent to monthly injections while dramatically reducing treatment burden in patients with DME.
- Although ocular surgery‑related adverse events were more frequent, serious vision‑threatening events were rare, and no PDS eyes developed endophthalmitis or retinal detachment.
- Continuous ranibizumab delivery with PDS offers an effective, durable alternative that may lessen clinic visit burden and improve real‑world adherence.