Time Course of Resolution of Diabetic Macular Edema by Sustained Suppression of VEGF-A with the Port Delivery Platform with Ranibizumab.
Abstract
Purpose
To determine the incidence of poor responsiveness to VEGF-A suppression in eyes with diabetic macular edema (DME) by evaluating the effect of continuous delivery of ranibizumab via the Port Delivery Platform with ranibizumab (PDS) in individual patients enrolled in the Pagoda clinical trial.
Design
Retrospective analysis of prospective clinical trial data SUBJECTS: DME patients enrolled in Pagoda (NCT04108156).
Methods
Change in central subfield thickness (CST) and best-corrected visual acuity (BCVA) over time was evaluated for the adjusted intent-to-treat (aITT) population in the Pagoda trial. Optical coherence tomography (OCT) images obtained at each visit were analyzed for 56 PDS subjects from 8 sites to determine the time course of changes in intraretinal and subretinal fluid. MAIN OUTCOME MEASURES CST, BCVA, and time to resolution of edema.
Results
In the aITT population the mean duration of follow up was 107.7 weeks in the PDS arm (n=272) and 100.7 weeks the IVT-PDS arm (n=238). The percentage of eyes with CST improvement into the normal range (≤325 µm) by the last visit was 87.9% in the PDS group and 85.3% in the IVT-PDS arm with mean time to normalization of 21.3 weeks and 20.6 weeks, respectively. All eyes in both arms showed reduction in CST over time although some exhibited periods of CST fluctuation and a few in each arm showed initial improvement followed by worsening at last follow up. In the eyes of 56 PDS patients that had detailed analysis of OCTs, normalization of CST occurred in 93% at a median of 17 weeks and elimination of intraretinal fluid in the central 1mm occurred in 84% at a median of 68 weeks. Only 3 of 56 eyes had poorly controlled DME at last follow up.
Conclusions
Sustained suppression of VEGF-A is sufficient to effectively treat DME in the vast majority of patients, but edema resolution may be slow in some patients giving the false impression of poor response to anti-VEGF-A treatment. In DME, the term unresponsive to anti-VEGF-A treatment should be replaced by slowly responsive.