Port Delivery System With Ranibizumab vs Monitoring in Nonproliferative Diabetic Retinopathy Without Macular Edema: The Pavilion Randomized Clinical Trial.

IMPORTANCE

Frequent prophylactic intravitreal anti-vascular endothelial growth factor injections can reduce risk of progression to vision-threatening complications in nonproliferative diabetic retinopathy (NPDR). A refillable drug delivery system for continuous intraocular ranibizumab release could offer less frequent treatment regimens.

OBJECTIVE

To evaluate the Port Delivery System (PDS) with ranibizumab, 100 mg/mL, with refill-exchange procedures every 36 weeks (PDS Q36W), vs no PDS (control) in moderately severe to severe NPDR without center-involved diabetic macular edema (CI-DME), monitoring both groups every 4 weeks.

DESIGN, SETTING, AND

PARTICIPANTS

This was a randomized clinical trial at 50 US investigational sites. Participants aged 18 years or older with moderately severe or severe NPDR (Diabetic Retinopathy Severity Scale [DRSS] level 47 or 53) secondary to type 1 or 2 diabetes were eligible. Data analysis was performed from August 10, 2020, to October 3, 2022.

INTERVENTION: Participants were randomized (unmasked) 5:3 to PDS Q36W vs control. Both groups could receive intravitreal ranibizumab injections if CI-DME, proliferative diabetic retinopathy (PDR), or anterior segment neovascularization (ASNV) developed.

MAIN OUTCOMES AND MEASURES: Proportion of participants with an improvement of at least 2 levels in Early Treatment Diabetic Retinopathy Study DRSS from baseline at week 52.

RESULTS

A total of 174 participants (mean [SD] age, 53.9 [11.7] years; 74 [42.5%] female) were randomized to PDS Q36W (n = 106) or control (n = 68). At week 52, 80.1% of those receiving PDS Q36W vs 9.0% of control participants had at least a 2-step DRSS improvement from baseline (difference, 71.1% [95% CI, 61.0% to 81.2%]; P < .001). Secondary outcomes included rate of development of CI-DME, PDR, or ASNV through week 52 (PDS Q36W, 7.1%; control, 47.0%; hazard ratio, 0.12 [95% CI, 0.05 to 0.28]; P < .001) and best-corrected visual acuity (BCVA) change from baseline to week 52 (+1.4 letters [95% CI, -0.5 to 3.3 letters] for those receiving PDS Q36W vs -2.6 letters [95% CI, -5.0 to -0.1 letters] for control participants; difference, 4.0 letters [95% CI, 0.9 to 7.1 letters]; P = .01). The PDS Q36W group had a transient BCVA decrease of 7.4 letters (95% CI, -10.3 to -4.5 letters) at 4 weeks after implantation, resolving 8 weeks later. Ocular adverse events of special interest occurred in 17 of 105 participants (16.2%) receiving PDS Q36W (cataract, 7 participants [6.7%]; vitreous hemorrhage, 6 participants [5.7%]; conjunctival bleb, conjunctival retraction, and hyphema, each 2 participants [1.9%]; conjunctival erosion and retinal detachment, each 1 participant [1.0%]), with no endophthalmitis reported through week 52.

CONCLUSIONS AND RELEVANCE: At 1 year, PDS Q36W resulted in substantially more participants achieving at least a 2-step DRSS improvement and a reduced risk of developing CI-DME, PDR, or ASNV compared with control participants, with safety outcomes consistent with previous reports. These findings should be balanced with the transient, postoperative decrease in BCVA 4 through 12 weeks after implantation and the need for longer-term BCVA and safety outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04503551.