Prevalence and Progression of Macular Atrophy in Eyes with Neovascular Age-Related Macular Degeneration in the Phase 2 Ladder Trial of the Port Delivery System with Ranibizumab

Purpose: To determine whether the rates of macular atrophy (MA) differ between eyes with neovascular age-related macular degeneration (nAMD) treated continuously with the Port Delivery System with ranibizumab (PDS) and those treated with ranibizumab given as a bolus intravitreal injection.

Design: A preplanned exploratory analysis of a phase 2, multicenter, randomized, active treatment-controlled, dose-ranging study.

Participants: Patients diagnosed with nAMD within 9 months of screening who had received at least 2 previous intravitreal anti-vascular endothelial growth factor injections of any agent and were responsive to the treatment.

Methods: Eyes were randomized (3:3:3:2) to treatment with either the PDS (filled with a customized formulation of ranibizumab at 10, 40, or 100 mg/ml and refilled pro re nata) or monthly intravitreal ranibizumab 0.5-mg injections.

Main outcome measures: The prevalence, incidence, and progression of MA.

Results: The analysis population consisted of 220 eyes (58, 62, 59, and 41 eyes in the PDS 10-mg/ml, 40-mg/ml, 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg injection arms, respectively). At study baseline, MA was observed in 14.5% (PDS 10-mg/ml), 11.5% (PDS 40-mg/ml), 13.6% (PDS 100-mg/ml), and 7.6% (monthly ranibizumab) of eyes. At the last assessment (mean, 22.1 months), the prevalence of MA had increased to 38.6% (PDS 10-mg/ml), 40.0% (PDS 40-mg/ml), 40.4% (PDS 100-mg/ml), and 45.7% (monthly ranibizumab). In patients without MA at baseline, a higher proportion of eyes in the monthly ranibizumab arm (40.6%) developed MA than in those in the PDS arms (28.6%, 32.1%, and 30.6% of eyes in the PDS 10-, 40-, and 100-mg/ml arms, respectively). The mean change in the area of MA from baseline to the last assessment for the PDS 10-mg/ml, 40-mg/ml, 100-mg/ml, and monthly ranibizumab arms was +2.46, +1.61, +1.09, and +1.15 mm², respectively. At 9 months, for patients without MA at baseline, the difference in the incidence of MA between the PDS 100-mg/ml and monthly ranibizumab groups was -12% (95% confidence interval, -31% to 7%).

Conclusions: In the phase 2 Ladder trial, there was no evidence of worse MA with the PDS compared with that with monthly intravitreal ranibizumab 0.5-mg injections. Larger trials focusing on MA are needed to confirm this finding.