Clinical Studies:


Summarized by Mrinali Gupta, MD (Retina Associates of Orange County)

Citation: Khanani AM, Callanan D, Dreyer R, et al. End of study results for the LADDER phase 2 trial of the port delivery system with ranibizumab for neovascular age-related macular degeneration. Ophthalmology Retina 2020; 5(8): 775-787.

Key Points

  • Over 22 months, vision and anatomical outcomes were similar between PDS-ranibizumab 100mg/mL and monthly intravitreal ranibizumab 0.5mg, with a mean time to first refill (amongst those needing any refills during the study period) of 8.8 months in the PDS-ranibizumab 100 mg/mL group.
  • Vitreous hemorrhage was the main complication with PDS treatment, with reduction in rates of vitreous hemorrhage (esp severe vitreous hemorrhage) after modification of the surgical PDS implantation technique, but still an overall rate of 5% vitreous hemorrhage with the modified technique. Vitreous hemorrhage in most cases was mild to moderate. Endophthalmitis rates were higher in the PDS group (1.7%).
  • Thus PDS-ranibizumab 100 mg/mL has the potential to significantly reduce treatment burden in patients with wet AMD, while maintaining similar vision and anatomical outcomes as gold-standard monthly treatment, albeit with increased risks related to the implantation procedure (hemorrhage) or the implant (endophthalmitis, conjunctival complications).
  • Objective

    To study the efficacy and safety of a port delivery system (PDS) for sustained delivery of ranibizumab for neovascular age-related macular degeneration (AMD)


    Phase 2, multicenter, randomized, treatment-controlled, dose-ranging trial of PDS versus monthly ranibizumab intravitreal injections


    Mean 22.1 (range 10.8-37.6) months

Clinical Trial Guide Video Thumb Watch VBS members discuss this study on New Retina Radio Journal Club

With Aleksandra Rachitskaya, MD; Mrinali Gupta, MD; Eric Nudleman, MD, PhD; and Aris Thanos, MD


Major inclusion criteria:


Randomized 3:3:3:2 to:

Randomization stratified by ETDRS letters (≤65 letters vs >66 letters) and # of prior anti-VEGF injections (≤3 or >3 injections)

PDS Procedure

Conjunctival peritomy, full thickness stab incision through sclera/pars plana with 3.2mm slit knife, followed by implantation of PDS implant, then conjunctival closure. Partway through the study, the procedure was amended to reduce vitreous hemorrhage risk to peritomy followed by layer-by-layer incision through sclera, then laser ablation of the exposed pars plana, followed by incision with the 3.2mm slit knife, etc.


All patients were monitored monthly. PDS patients underwent refill (full exchange/refill) procedures in the office under topical anesthesia based on one or more prespecified criteria including:

Intravitreal ranibizumab injections were also available to PDS patients if vitreous hemorrhage occurred with BCVA loss with inability to assess macula or SD-OCT, if lack of clinical efficacy criteria met, or if progressively worsening BCVA or CFT on 2 consecutive visits due to nAMD that did not hit threshold for refill. If lack of clinical efficacy criteria met, implant was retained, received intravitreal ranibizumab 0.5mg injection and mandatory refill of implant with ranibizumab 100mg/mL at the next monthly visit (and all future refills were 100mg/mL).

After the primary LADDER study analysis, all patients continued their assigned treatment until PORTAL (open label PDS extension study) initiated. If patients did not rollover into PORTAL, PDS was removed

RESULTS (24 months)

Study population

Study Duration

Time to refill analysis

PDS-ranibizumab 10mg/mL: 8.7 months

PDS-ranibizumab 40mg/mL: 13 months

PDS-ranibizumab 100mg/mL: 15.8 months

(significantly better for 40 and 100mg/mL compared to 10mg/mL)

Additional refill analysis

PDS-ranibizumab 10mg/mL: 65.5%

PDS-ranibizumab 40mg/mL: 54.8%

PDS-ranibizumab 100mg/mL: 52.5%

In this subset, mean time to refill was:

PDS-ranibizumab 10mg/mL: 6.4 months

PDS-ranibizumab 40mg/mL: 5.6 months

PDS-ranibizumab 100mg/mL: 8.8 months

In this subset, time from first to second refill was:

PDS-ranibizumab 10mg/mL: 3.3 months

PDS-ranibizumab 40mg/mL: 5.9 months

PDS-ranibizumab 100mg/mL: 8.8 months

Vision outcomes:

PDS-ranibizumab 10mg/mL: -4.6 letters

PDS-ranibizumab 40mg/mL: -2.3 letters

PDS-ranibizumab 100mg/mL: +2.9 letters

monthly ranibizumab 0.5mg injection: +2.7 letters

PDS-ranibizumab 10mg/mL: 57.7%

PDS-ranibizumab 40mg/mL: 80%

PDS-ranibizumab 100mg/mL: 87.5%

monthly ranibizumab 0.5mg injection: 88.9%

Anatomic outcomes

Adverse outcomes